Journal of Neurophysiology recent issues

Preprint Servers and the Journal of Neurophysiology

Linden, D. J. — Wed, 04 Nov 2009 11:06:50 PST

Top-Down Control of Saccades as Part of a Generalized Model of Proactive Inhibitory Control

Ballanger, B. — Wed, 04 Nov 2009 11:06:50 PST

Lo and colleagues have recently described a recurrent network model of inhibitory control of saccadic eye movements based on neurophysiological observations in the frontal eye field (FEF) and superior colliculus (SC) of rhesus monkeys. This model emphasizes the proactive, inhibition-based, tonic neuronal activity that prevents the eye from moving in a countermanding paradigm. In this review I discuss the model with respect to existing literature that the authors did not mention, suggesting that proactive inhibitory control extends far beyond saccadic control and provides an interesting framework to interpret several attentional and movement disorders in humans.

Exploring the Superior Colliculus In Vitro

Isa, T., Hall, W. C. — Wed, 04 Nov 2009 11:06:50 PST

The superior colliculus plays an important role in the translation of sensory signals that encode the location of objects in space into motor signals that encode vectors of the shifts in gaze direction called saccades. Since the late 1990s, our two laboratories have been applying whole cell patch-clamp techniques to in vitro slice preparations of rodent superior colliculus to analyze the structure and function of its circuitry at the cellular level. This review describes the results of these experiments and discusses their contributions to our understanding of the mechanisms responsible for sensorimotor integration in the superior colliculus. The experiments analyze vertical interactions between its superficial visuosensory and intermediate premotor layers and propose how they might contribute to express saccades and to saccadic suppression. They also compare and contrast the circuitry within each of these layers and propose how this circuitry might contribute to the selection of the targets for saccades and to the build-up of the premotor commands that precede saccades. Experiments also explore in vitro the roles of extrinsic inputs to the superior colliculus, including cholinergic inputs from the parabigeminal and parabrachial nuclei and GABAergic inputs from the substantia nigra pars reticulata, in modulating the activity of the collicular circuitry. The results extend and clarify our understanding of the multiple roles the superior colliculus plays in sensorimotor integration.

Surround Motion Silences Signals From Same-Direction Motion

Neri, P., Levi, D. — Wed, 04 Nov 2009 11:06:50 PST

The response of motion-sensitive neurons to stimuli presented within their receptive field is often affected by stimulation in the surrounding region. These effects have perceptually relevant consequences that can be measured using behavioral techniques. We used psychophysical reverse correlation to characterize directional selectivity in human observers while they processed a local motion stimulus and studied the effect of adding an additional motion signal in the surrounding region. The surround had no effect on response gain for signals of opposite direction but selectively reduced gain for those of same direction. Surprisingly this reduction was close to 100%, effectively amounting to a gating process whereby signals of same direction were completely silenced. Our data indicate that by far the most prominent perceptual manifestation of center-surround antagonism is gain suppression by motion in the same direction without any appreciable change in directional tuning.

Organization of Hue Selectivity in Macaque V2 Thin Stripes

Lim, H., Wang, Y., Xiao, Y., Hu, M., Felleman, D. J. — Wed, 04 Nov 2009 11:06:50 PST

V2 has long been recognized to contain functionally distinguishable compartments that are correlated with the stripelike pattern of cytochrome oxidase activity. Early electrophysiological studies suggested that color, direction/disparity, and orientation selectivity were largely segregated in the thin, thick, and interstripes, respectively. Subsequent studies revealed a greater degree of homogeneity in the distribution of response properties across stripes, yet color-selective cells were still found to be most prevalent in the thin stripes. Optical recording studies have demonstrated that thin stripes contain both color-preferring and luminance-preferring modules. These thin stripe color-preferring modules contain spatially organized hue maps, whereas the luminance-preferring modules contain spatially organized luminance-change maps. In this study, the neuronal basis of these hue maps was determined by characterizing the selectivity of neurons for isoluminant hues in multiple penetrations within previously characterized V2 thin stripe hue maps. The results indicate that neurons within the superficial layers of V2 thin stripe hue maps are organized into columns whose aggregated hue selectivity is closely related to the hue selectivity of the optically defined hue maps. These data suggest that thin stripes contain hue maps not simply because of their moderate percentage of hue-selective neurons, but because of the columnar and tangential organization of hue selectivity.

Dependence of the Roll Angular Vestibuloocular Reflex (aVOR) on Gravity

Yakushin, S. B., Xiang, Y., Cohen, B., Raphan, T. — Wed, 04 Nov 2009 11:06:50 PST

Little is known about the dependence of the roll angular vestibuloocular reflex (aVOR) on gravity or its gravity-dependent adaptive properties. To study gravity-dependent characteristics of the roll aVOR, monkeys were oscillated about a naso-occipital axis in darkness while upright or tilted. Roll aVOR gains were largest in the upright position and decreased by 7–15% as animals were tilted from the upright. Thus the unadapted roll aVOR gain has substantial gravitational dependence. Roll gains were also decreased or increased by 0.25 Hz, in- or out-of-phase rotation of the head and the visual surround while animals were prone, supine, upright, or in side-down positions. Gain changes, determined as a function of head tilt, were fit with a sinusoid; the amplitudes represented the amount of the gravity-dependent gain change, and the bias, the gravity-independent gain change. Gravity-dependent gain changes were absent or substantially smaller in roll (5%) than in yaw (25%) or pitch (17%), whereas gravity-independent gain changes were similar for roll, pitch, and yaw (20%). Thus the high-frequency roll aVOR gain has an inherent dependence on head orientation re gravity in the unadapted state, which is different from the yaw/pitch aVORs. This inherent gravitational dependence may explain why the adaptive circuits are not active when the head is tilted re gravity during roll aVOR adaptation. These behavioral differences support the idea that there is a fundamental difference in the central organization of canal-otolith convergence of the roll and yaw/pitch aVORs.

Context-Dependent Effects of NMDA Receptors on Precise Timing Information at the Endbulb of Held in the Cochlear Nucleus

Pliss, L., Yang, H., Xu-Friedman, M. A. — Wed, 04 Nov 2009 11:06:50 PST

Many synapses contain both AMPA receptors (AMPAR) and N-methyl-d-aspartate receptors (NMDAR), but their different roles in synaptic computation are not clear. We address this issue at the auditory nerve fiber synapse (called the endbulb of Held), which is formed on bushy cells of the cochlear nucleus. The endbulb refines and relays precise temporal information to nuclei responsible for sound localization. The endbulb has a number of specializations that aid precise timing, including AMPAR-mediated excitatory postsynaptic currents (EPSCs) with fast kinetics. Voltage-clamp experiments in mouse brain slices revealed that slow NMDAR EPSCs are maintained at mature endbulbs, contributing a peak conductance of around 10% of the AMPAR-mediated EPSC. During repetitive synaptic activity, AMPAR EPSCs depressed and NMDAR EPSCs summated, thereby increasing the relative importance of NMDARs. This could impact temporal precision of bushy cells because of the slow kinetics of NMDARs. We tested this by blocking NMDARs and quantifying bushy cell spike timing in current clamp when single endbulbs were activated. These experiments showed that NMDARs contribute to an increased probability of firing, shorter latency, and reduced jitter. Dynamic-clamp experiments confirmed this effect and showed it was dose-dependent. Bushy cells can receive inputs from multiple endbulbs. When we applied multiple synaptic inputs in dynamic clamp, NMDARs had less impact on spike timing. NMDAR conductances much higher than mature levels could disrupt spiking, which may explain its downregulation during development. Thus mature NMDAR expression can support the conveying of precise temporal information at the endbulb, depending on the stimulus conditions.

Long-Lasting Context Dependence Constrains Neural Encoding Models in Rodent Auditory Cortex

Asari, H., Zador, A. M. — Wed, 04 Nov 2009 11:06:50 PST

Acoustic processing requires integration over time. We have used in vivo intracellular recording to measure neuronal integration times in anesthetized rats. Using natural sounds and other stimuli, we found that synaptic inputs to auditory cortical neurons showed a rather long context dependence, up to ≥4 s ( ~ 1 s), even though sound-evoked excitatory and inhibitory conductances per se rarely lasted 100 ms. Thalamic neurons showed only a much faster form of adaptation with a decay constant <100 ms, indicating that the long-lasting form originated from presynaptic mechanisms in the cortex, such as synaptic depression. Restricting knowledge of the stimulus history to only a few hundred milliseconds reduced the predictable response component to about half that of the optimal infinite-history model. Our results demonstrate the importance of long-range temporal effects in auditory cortex and suggest a potential neural substrate for auditory processing that requires integration over timescales of seconds or longer, such as stream segregation.

Time Course of Activity in Itch-Related Brain Regions: A Combined MEG-fMRI Study

Wed, 04 Nov 2009 11:06:51 PST

Functional neuroimaging studies have identified itch-related brain regions. However, no study has investigated the temporal aspect of itch-related brain processing. Here this issue was investigated using electrically evoked itch in ten healthy adults. Itch stimuli were applied to the left wrist and brain activity was measured using magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI). In the MEG experiment, the magnetic responses evoked by the itch stimuli were observed in the contralateral and ipsilateral frontotemporal regions. The dipoles associated with the magnetic responses were mainly located in the contralateral (nine subjects) and ipsilateral (eight subjects) secondary somatosensory cortex (SII)/insula, which were also activated by the itch stimuli in the fMRI experiment. We also observed an itch-related magnetic response in the posterior part of the centroparietal region in six subjects. MEG and fMRI data showed that the magnetic response in this region was mainly associated with itch-related activation of the precuneus. The latency was significantly longer in the ipsilateral than that in the contralateral SII/insula, suggesting the difference to be associated with transmission in the callosal fibers. The timing of activation of the precuneus was between those of the contralateral and ipsilateral SII/insula. Other sources were located in the premotor, primary motor, and anterior cingulate cortices (one subject each). This study is the first to demonstrate part of the time course of itch-related brain processing. Combining methods with high temporal and spatial resolution (e.g., MEG and fMRI) would be useful to investigate the temporal aspect of the brain mechanism of itch.

Asymmetric Changes in Cutaneous Reflexes After a Partial Spinal Lesion and Retention Following Spinalization During Locomotion in the Cat

Frigon, A., Barriere, G., Leblond, H., Rossignol, S. — Wed, 04 Nov 2009 11:06:51 PST

Locomotion involves dynamic interactions between the spinal cord, supraspinal signals, and peripheral sensory inputs. After incomplete spinal cord injury (SCI), interactions are disrupted, and remnant structures must optimize function to maximize locomotion. We investigated if cutaneous reflexes are altered following a unilateral partial spinal lesion and whether changes are retained within spinal circuits after complete spinal transection (i.e., spinalization). Four cats were chronically implanted with recording and stimulating electrodes. Cutaneous reflexes were evoked with cuff electrodes placed around left and right superficial peroneal nerves. Control data, consisting of hindlimb kinematics and electromyography (bursts of muscular activity and cutaneous reflexes), were recorded during treadmill locomotion. After stable control data were achieved (53–67 days), a partial spinal lesion was made at the 10th or 11th thoracic segment (T₁₀–T₁₁) on the left side. Cats were trained to walk after the partial lesion, and following a recovery period (64–80 days), a spinalization was made at T₁₃. After the partial lesion, changes in short-latency excitatory (P1) homologous responses between hindlimbs, evoked during swing, were largely asymmetric in direction relative to control values, whereas changes in longer-latency excitatory (P2) and crossed responses were largely symmetric in direction. After spinalization, cats could display hindlimb locomotion within 1 day. Early after spinalization, reflex changes persisted a few days, but over time homologous P1 responses increased symmetrically toward or above control levels. Therefore changes in cutaneous reflexes after the partial lesion and retention following spinalization indicate an important spinal plasticity after incomplete SCI.

Eye-Hand Coordination During Target Selection in a Pop-Out Visual Search

Song, J.-H., McPeek, R. M. — Wed, 04 Nov 2009 11:06:51 PST

We examined the coordination of saccades and reaches in a visual search task in which monkeys were rewarded for reaching to an odd-colored target among distractors. Eye movements were unconstrained, and monkeys typically made one or more saccades before initiating a reach. Target selection for reaching and saccades was highly correlated with the hand and eyes landing near the same final stimulus both for correct reaches to the target and for incorrect reaches to a distractor. Incorrect reaches showed a bias in target selection: they were directed to the distractor in the same hemifield as the target more often than to other distractors. A similar bias was seen in target selection for the initial saccade in correct reaching trials with multiple saccades. We also examined the temporal coupling of saccades and reaches. In trials with a single saccade, a reaching movement was made after a fairly stereotyped delay. In multiple-saccade trials, a reach to the target could be initiated near or even before the onset of the final target-directed saccade. In these trials, the initial trajectory of the reach was often directed toward the fixated distractor before veering toward the target around the time of the final saccade. In virtually all cases, the eyes arrived at the target before the hand, and remained fixated until reach completion. Overall, these results are consistent with flexible temporal coupling of saccade and reach initiation, but fairly tight coupling of target selection for the two types of action.

Effects of Canal Plugging on the Vestibuloocular Reflex and Vestibular Nerve Discharge During Passive and Active Head Rotations

Sadeghi, S. G., Goldberg, J. M., Minor, L. B., Cullen, K. E. — Wed, 04 Nov 2009 11:06:51 PST

Mechanical occlusion (plugging) of the slender ducts of semicircular canals has been used in the clinic as well as in basic vestibular research. Here, we investigated the effect of canal plugging in two macaque monkeys on the horizontal vestibuloocular reflex (VOR) and the responses of vestibular-nerve afferents during passive head rotations. Afferent responses to active head movements were also studied. The horizontal VOR gain decreased after plugging to <0.1 for frequencies <2 Hz but rose to about 0.6 as frequency was increased to 15 Hz. Afferents innervating plugged horizontal canals had response sensitivities that increased with the frequency of passive rotations from <0.01 (spikes/s)/(°/s) at 0.5 Hz to values of about 0.2 and 0.5 (spikes/s)/(°/s) at 8 Hz for regular and irregular afferents, respectively (<50% of responses in controls). An increase in phase lead was also noted following plugging in afferent discharge, but not in the VOR. Because the phase discrepancy between the VOR and afferent discharge is much larger than that seen in control animals, this suggests that central adaptation shapes VOR dynamics following plugging. The effect of canal plugging on afferent responses can be modeled as an increase in stiffness and a reduction in the dominant time constant and gain in the transfer function describing canal dynamics. Responses were also evident during active head rotations, consistent with the frequency content of these movements. We conclude that canal plugging in macaques is effective only at frequencies <2 Hz. At higher frequencies, afferents show significant responses, with a nearly 90° phase lead, such that they encode near-rotational acceleration. Our results demonstrate that afferents innervating plugged canals respond robustly during voluntary movements, a finding that has implications for understanding the effects of canal plugging in clinical practice.

Visual Field Maps, Population Receptive Field Sizes, and Visual Field Coverage in the Human MT+ Complex

Amano, K., Wandell, B. A., Dumoulin, S. O. — Wed, 04 Nov 2009 11:06:51 PST

Human neuroimaging experiments typically localize motion-selective cortex (MT+) by contrasting responses to stationary and moving stimuli. It has long been suspected that MT+, located on the lateral surface at the temporal–occipital (TO) boundary, contains several distinct visual field maps, although only one coarse map has been measured. Using a novel functional MRI model–based method we identified two maps—TO-1 and TO-2—and measured population receptive field (pRF) sizes within these maps. The angular representation of the first map, TO-1, has a lower vertical meridian on its posterior side at the boundary with the lateral–occipital cortex (i.e., the LO-2 portion). The angular representation continues through horizontal to the upper vertical meridian at the boundary with the second map, TO-2. The TO-2 angle map reverses from upper to lower visual field at increasingly anterior positions. The TO maps share a parallel eccentricity map in which center-to-periphery is represented in the ventral-to-dorsal direction; both maps have an expanded foveal representation. There is a progressive increase in the pRF size from V1/2/3 to LO-1/2 and TO-1/2, with the largest pRF sizes in TO-2. Further, within each map the pRF size increases as a function of eccentricity. The visual field coverage of both maps extends into the ipsilateral visual field, with larger sensitivity to peripheral ipsilateral stimuli in TO-2 than that in TO-1. The TO maps provide a functional segmentation of human motion-sensitive cortex that enables a more complete characterization of processing in human motion-selective cortex.

Brain Switch for Reflex Micturition Control Detected by fMRI in Rats

Wed, 04 Nov 2009 11:06:51 PST

The functions of the lower urinary tract are controlled by complex pathways in the brain that act like switching circuits to voluntarily or reflexly shift the activity of various pelvic organs (bladder, urethra, urethral sphincter, and pelvic floor muscles) from urine storage to micturition. In this study, functional magnetic resonance imaging (fMRI) was used to visualize the brain switching circuits controlling reflex micturition in anesthetized rats. The fMRI images confirmed the hypothesis based on previous neuroanatomical and neurophysiological studies that the brain stem switch for reflex micturition control involves both the periaqueductal gray (PAG) and the pontine micturition center (PMC). During storage, the PAG was activated by afferent input from the urinary bladder while the PMC was inactive. When bladder volume increased to the micturition threshold, the switch from storage to micturition was associated with PMC activation and enhanced PAG activity. A complex brain network that may regulate the brain stem micturition switch and control storage and voiding was also identified. Storage was accompanied by activation of the motor cortex, somatosensory cortex, cingulate cortex, retrosplenial cortex, thalamus, putamen, insula, and septal nucleus. On the other hand, micturition was associated with: 1) increased activity of the motor cortex, thalamus, and putamen; 2) a shift in the locus of activity in the cingulate and insula; and 3) the emergence of activity in the hypothalamus, substantia nigra, globus pallidus, hippocampus, and inferior colliculus. Understanding brain control of reflex micturition is important for elucidating the mechanisms underlying neurogenic bladder dysfunctions including frequency, urgency, and incontinence.

Neural Representations of Complex Temporal Modulations in the Human Auditory Cortex

Ding, N., Simon, J. Z. — Wed, 04 Nov 2009 11:06:51 PST

Natural sounds such as speech contain multiple levels and multiple types of temporal modulations. Because of nonlinearities of the auditory system, however, the neural response to multiple, simultaneous temporal modulations cannot be predicted from the neural responses to single modulations. Here we show the cortical neural representation of an auditory stimulus simultaneously frequency modulated (FM) at a high rate, f_FM 40 Hz, and amplitude modulation (AM) at a slow rate, f_AM <15 Hz. Magnetoencephalography recordings show fast FM and slow AM stimulus features evoke two separate but not independent auditory steady-state responses (aSSR) at f_FM and f_AM, respectively. The power, rather than phase locking, of the aSSR of both decreases with increasing stimulus f_AM. The aSSR at f_FM is itself simultaneously amplitude modulated and phase modulated with fundamental frequency f_AM, showing that the slow stimulus AM is not only encoded in the neural response at f_AM but also encoded in the instantaneous amplitude and phase of the neural response at f_FM. Both the amplitude modulation and phase modulation of the aSSR at f_FM are most salient for low stimulus f_AM but remain observable at the highest tested f_AM (13.8 Hz). The instantaneous amplitude of the aSSR at f_FM is successfully predicted by a model containing temporal integration on two time scales, ~25 and ~200 ms, followed by a static compression nonlinearity.

Age-Related Declines in Visuospatial Working Memory Correlate With Deficits in Explicit Motor Sequence Learning

Bo, J., Borza, V., Seidler, R. D. — Wed, 04 Nov 2009 11:06:51 PST

Numerous studies have shown that older adults exhibit deficits in motor sequence learning, but the mechanisms underlying this effect remain unclear. Our recent work has shown that visuospatial working-memory capacity predicts the rate of motor sequence learning and the length of motor chunks formed during explicit sequence learning in young adults. In the current study, we evaluate whether age-related deficits in working memory explain the reduced rate of motor sequence learning in older adults. We found that older adults exhibited a correlation between visuospatial working-memory capacity and motor sequence chunk length, as we observed previously in young adults. In addition, older adults exhibited an overall reduction in both working-memory capacity and motor chunk length compared with that of young adults. However, individual variations in visuospatial working-memory capacity did not correlate with the rate of learning in older adults. These results indicate that working memory declines with age at least partially explain age-related differences in explicit motor sequence learning.

Changing the "When" and "What" of Intended Actions

Obhi, S. S., Matkovich, S., Chen, R. — Wed, 04 Nov 2009 11:06:51 PST

Humans often have to modify the timing and/or type of their planned actions on the basis of new sensory information. In the present experiments, participants planned to make a right index finger keypress 3 s after a warning stimulus but on some trials were interrupted by a temporally unpredictable auditory tone prompting the same action (experiment 1) or a different action (experiment 2). In experiment 1, by comparing the reaction time (RT) to tones presented at different stages of the preparatory period to RT in a simple reaction time condition, we determined the cost of switching from an internally generated mode of response production to an externally triggered mode in situations requiring only a change in when an action is made (i.e., when the tone prompts the action at a different time from the intended time of action). Results showed that the cost occurred for interruption tones delivered 200 ms after a warning stimulus and remained relatively stable throughout most of the preparatory period with a reduction in the magnitude of the cost during the last 200 ms prior to the intended time of movement. In experiment 2, which included conditions requiring a change in both when and what action is produced on the tone, results show a larger cost when the switched to action is different from the action being prepared. We discuss our results in the light of neurophysiological experiments on motor preparation and suggest that intending to act is accompanied by a general inhibitory mechanism preventing premature motor output and a specific excitatory process pertaining to the intended movement. Interactions between these two mechanisms could account for our behavioral results.

Intrinsic Neuronal Excitability Is Reversibly Altered by a Single Experience in Fear Conditioning

McKay, B. M., Matthews, E. A., Oliveira, F. A., Disterhoft, J. F. — Wed, 04 Nov 2009 11:06:51 PST

Learning is known to cause alterations in intrinsic cellular excitability but, to date, these changes have been seen only after multiple training trials. A powerful learning task that can be quickly acquired and extinguished with a single trial is fear conditioning. Rats were trained and extinguished on a hippocampus-dependent form of fear conditioning to determine whether learning-related changes in intrinsic excitability could be observed after a few training trials and a single extinction trial. Following fear training, hippocampal slices were made and intrinsic excitability was assayed via whole cell recordings from CA1 neurons. Alterations in intrinsic excitability, assayed by the postburst afterhyperpolarization and firing frequency accommodation, were observed after only three trials of contextual or trace-cued fear conditioning. Animals that had been trained in contextual and trace-cued fear were then extinguished. Context fear-conditioned animals extinguished in a single trial and the changes in intrinsic excitability were reversed. Trace-cue conditioned animals only partially extinguished in a single trial and reductions in excitability remained. Thus a single learning experience is sufficient to alter intrinsic excitability. This dramatically extends observations of learning-specific changes in intrinsic neuronal excitability previously observed in paradigms requiring many training trials, suggesting the excitability changes have a basic role in acquiring new information.

Transformation in the Neural Code for Whisker Deflection Direction Along the Lemniscal Pathway

Bale, M. R., Petersen, R. S. — Wed, 04 Nov 2009 11:06:51 PST

A prominent characteristic of neurons in the whisker system is their selectivity to the direction in which a whisker is deflected. The aim of this study was to determine how information about whisker direction is encoded at successive levels of the lemniscal pathway. We made extracellular recordings under identical conditions from the trigeminal ganglion, ventro-posterior medial thalamus (VPM), and barrel cortex while varying the direction of whisker deflection. We found a marked increase in the variability of single unit responses along the pathway. To study the consequences of this for information processing, we quantified the responses using mutual information. VPM units conveyed 48% of the mutual information conveyed by ganglion units, and cortical units conveyed 12%. The fraction of neuronal bandwidth used for transmitting direction information decreased from 40% in the ganglion to 24% in VPM and 5% in barrel cortex. To test whether, in cortex, population coding might compensate for this information loss, we made simultaneous recordings. We found that cortical neuron pairs conveyed 2.1 times the mutual information conveyed by single neurons. Overall, these findings indicate a marked transformation from a subcortical neural code based on small numbers of reliable neurons to a cortical code based on populations of unreliable neurons. However, the basic form of the neural code in ganglion, thalamus, and cortex was similar—at each stage, the first poststimulus spike carried the majority of the information.

Question of Reference Frames: Visual Direction-Selective Neurons in the Accessory Optic System of Goldfish

Masseck, O. A., Hoffmann, K.-P. — Wed, 04 Nov 2009 11:06:51 PST

We investigated if visual direction-selective neurons in the pretectal area (APT) of goldfish (Carassius auratus auratus) preferred visual stimuli resulting from rotations around axes corresponding to the best responsive axes of the semicircular canals [optic flow that is consistent to a maximal activation of the horizontal canal pair (yaw), to a maximal activation of the right anterior/left posterior semicircular canal pair (RALP), and to a maximal activation of the left anterior/right posterior semicircular canal pair (LARP)]. Our sample of neurons recorded in the left pretectum had two preferred axes of rotation: first, rotation around the yaw axis and second, rotation around the RALP axis. Both axes of rotation correspond to best responsive axes of the semicircular canals. For this reason, coding in a reference frame defined by the vestibular system or the pulling direction of the eye muscles is suggested. In our population of recorded APT neurons, we did not find segregation of different preferred axes of rotation into different anatomical structures. Furthermore in all axes no bias for clockwise or counterclockwise rotations was obvious. This is particularly noteworthy for the yaw axis because preference for temporo-nasal and naso-temporal rotations was found at the same recording side. Hence we conclude that in fish the accessory optic system may consist of one nucleus on each side of the midbrain only, the APT. Segregation into different nuclei coding for different axes and different senses of rotation probably first developed in amphibians.

Generalization of Visuomotor Learning Between Bilateral and Unilateral Conditions

Wang, J., Sainburg, R. L. — Wed, 04 Nov 2009 11:06:51 PST

A long history of behavioral and physiological research has suggested that bilateral coordination invokes unique neural processes that are not involved in unilateral movements. This hypothesis predicts that motor learning should show limited transfer between unilateral and bilateral conditions, which is consistent with a recent finding that indicated partial, but not complete, transfer of learning between the two conditions. However, during learning of new motor skills, transformations must also be made between visual and proprioceptive coordinate systems, a process that may occur upstream to the processes that differentiate bilateral from unilateral movements. We now investigate whether visuomotor adaptations are shared between unilateral and bilateral movement conditions. Our results indicate substantial transfer from bilateral to subsequent unilateral conditions for both arms. Interestingly, whereas the nondominant arm never showed complete adaptation to visual rotation under bilateral conditions, this interference, or lack of improvement, in bilateral performance did not disturb the visuomotor adaptation process or transfer, as reflected by superb unilateral performances immediately following the bilateral conditions. These findings unambiguously indicate that visuomotor adaptation can extensively generalize between bilateral and unilateral conditions, thus suggesting a substantial overlap in the neural processes underlying visuomotor transformations between the two movement conditions. Our findings provide support for a two-stage model of motor planning, in which the visuomotor transformation process precedes the processes that convert the visuomotor plan into effector-specific commands that incorporate bilateral synergies and that result in the forces that determine motion.

On the Open-Loop and Feedback Processes That Underlie the Formation of Trajectories During Visual and Nonvisual Locomotion in Humans

Pham, Q.-C., Hicheur, H. — Wed, 04 Nov 2009 11:06:51 PST

We investigated the nature of the control mechanisms at work during goal-oriented locomotion. In particular, we tested the effects of vision, locomotor speed, and the presence of via points on the geometric and kinematic properties of locomotor trajectories. We first observed that the average trajectories recorded in visual and nonvisual locomotion were highly comparable, suggesting the existence of vision-independent processes underlying the formation of locomotor trajectories. Then by analyzing and comparing the variability around the average trajectories across different experimental conditions, we were able to demonstrate the existence of on-line feedback control in both visual and nonvisual locomotion and to clarify the relations between visual and nonvisual control strategies. Based on these insights, we designed a model in which maximum-smoothness and optimal feedback control principles account, respectively, for the open-loop and feedback processes. Taken together, the experimental and modeling findings provide a novel understanding of the nature of the motor, sensory, and "navigational" processes underlying goal-oriented locomotion.

Transfer of Dynamic Learning Across Postures

Ahmed, A. A., Wolpert, D. M. — Wed, 04 Nov 2009 11:06:51 PST

When learning a difficult motor task, we often decompose the task so that the control of individual body segments is practiced in isolation. But on re-composition, the combined movements can result in novel and possibly complex internal forces between the body segments that were not experienced (or did not need to be compensated for) during isolated practice. Here we investigate whether dynamics learned in isolation by one part of the body can be used by other parts of the body to immediately predict and compensate for novel forces between body segments. Subjects reached to targets while holding the handle of a robotic, force-generating manipulandum. One group of subjects was initially exposed to the novel robot dynamics while seated and was then tested in a standing position. A second group was tested in the reverse order: standing then sitting. Both groups adapted their arm dynamics to the novel environment, and this movement learning transferred between seated and standing postures and vice versa. Both groups also generated anticipatory postural adjustments when standing and exposed to the force field for several trials. In the group that had learned the dynamics while seated, the appropriate postural adjustments were observed on the very first reach on standing. These results suggest that the CNS can immediately anticipate the effect of learned movement dynamics on a novel whole-body posture. The results support the existence of separate mappings for posture and movement, which encode similar dynamics but can be adapted independently.

5-HT and GABA Modulate Intrinsic Excitability of Type I Interneurons in Hermissenda

Jin, N. G., Tian, L.-M., Crow, T. — Wed, 04 Nov 2009 11:06:51 PST

The sensory neurons (photoreceptors) in the visual system of Hermissenda are one site of plasticity produced by Pavlovian conditioning. A second site of plasticity produced by conditioning is the type I interneurons in the cerebropleural ganglia. Both photoreceptors and statocyst hair cells of the graviceptive system form monosynaptic connections with identified type I interneurons. Two proposed neurotransmitters in the graviceptive system, serotonin (5-HT) and -aminobutyric acid (GABA), have been shown to modify synaptic strength and intrinsic neuronal excitability in identified photoreceptors. However, the potential role of 5-HT and GABA in plasticity of type I interneurons has not been investigated. Here we show that 5-HT increased the peak amplitude of light-evoked complex excitatory postsynaptic potentials (EPSPs), enhanced intrinsic excitability, and increased spike activity of identified type I_e(A) interneurons. In contrast, 5-HT decreased spike activity and intrinsic excitability of type I_e(B) interneurons. The classification of two categories of type I_e interneurons was also supported by the observation that 5-HT produced opposite effects on whole cell steady-state outward currents in type I_e interneurons. Serotonin produced a reduction in the amplitude of light-evoked complex inhibitory PSPs (IPSPs), increased spontaneous spike activity, decreased intrinsic excitability, and depolarized the resting membrane potential of identified type I_i interneurons. In contrast to the effects of 5-HT, GABA produced inhibition in both types of I_e interneurons and type I_i interneurons. These results show that 5-HT and GABA can modulate the intrinsic excitability of type I interneurons independent of the presynaptic effects of the same transmitters on excitability and synaptic efficacy of photoreceptors.

Distinct Electrophysiological Properties in Subtypes of Nonspiking Olfactory Local Interneurons Correlate With Their Cell Type-Specific Ca2+ Current Profiles

Husch, A., Paehler, M., Fusca, D., Paeger, L., Kloppenburg, P. — Wed, 04 Nov 2009 11:06:51 PST

A diverse population of local interneurons (LNs) helps to process, structure, and spatially represent olfactory information in the insect antennal lobe. In Periplaneta americana, we identified two subtypes of nonspiking local interneurons (type II LNs) by their distinct morphological and intrinsic electrophysiological properties. As an important step toward a better understanding of the cellular mechanisms that mediate odor information processing, we present a detailed analysis of their distinct voltage-activated Ca²⁺ currents, which clearly correlated with their distinct intrinsic electrophysiological properties. Both type II LNs did not posses voltage-activated Na⁺ currents and apparently innervated all glomeruli including the macroglomerulus. Type IIa LNs had significant longer and thicker low-order neurites and innervated each glomerulus entirely and homogeneously, whereas type IIb LNs innervated only parts of each glomerulus. All type II LNs were broadly tuned and responded to odorants of many chemical classes with graded changes in the membrane potential. Type IIa LNs responded with odor-specific elaborate patterns of excitation that could also include "spikelets" riding on the depolarizations and periods of inhibition. In contrast, type IIb LNs responded mostly with sustained, relatively smooth depolarizations. Consistent with the strong active membrane properties of type IIa LNs versus type IIb LNs, the voltage-activated Ca²⁺ current of type IIa LNs activated at more hyperpolarized membrane potentials and had a larger transient component.

Influence of Vagotomy on Monosynaptic Transmission at Second-Order Nucleus Tractus Solitarius Synapses

Swartz, J. B., Weinreich, D. — Wed, 04 Nov 2009 11:06:51 PST

Manipulations of vagal activity are used to treat medical pathologies, but the underlying CNS changes caused by these treatments are not well understood. Furthermore, heart and lung transplant as well as treatments for many gastrointestinal disorders result in section of the vagus nerve (vagotomy). Following unilateral vagotomy under isoflurane anesthesia of Sprague-Dawley rats, electrophysiological properties were recorded with whole cell patch techniques in horizontal brain stem slices. Vagotomy significantly reduced the median amplitude of evoked excitatory postsynaptic currents (evEPSCs; –121; n = 43) in the nucleus tractus solitarius (NTS) when compared with controls (–157 pA; n = 66; P < 0.05) but had no significant effect on the passive properties or on the average amplitude or frequency of miniature EPSCs. The degree of synaptic failure exhibited during a 50-Hz train of stimuli was used to define two separate classes of synapses: "low failure" and "high failure" (HF); failure rates <5 and ≥5%, respectively. HF synapses had significantly smaller median evEPSCs (–88 vs. –184 pA; P < 0.05). After vagotomy, the percentage of HF synapses nearly doubled to 56% (n = 24/43) when compared with controls (30%; n = 20/66). Additionally, the overall percentage of failures after the second to fifth stimuli significantly increased by at least twofold. These results suggest that vagotomy causes a decrease in synaptic efficacy by both increasing the overall percentage of synaptic failures and shifting the population of NTS synapses toward more HF transmission. In addition, the alterations due to vagotomy are likely to be presynaptic in nature.

Bilateral Limb Phase Relationship and Its Potential to Alter Muscle Activity Phasing During Locomotion

Alibiglou, L., Lopez-Ortiz, C., Walter, C. B., Brown, D. A. — Wed, 04 Nov 2009 11:06:51 PST

It is well established that the sensorimotor state of one limb can influence another limb and therefore bilateral somatosensory inputs make an important contribution to interlimb coordination patterns. However, the relative contribution of interlimb pathways for modifying muscle activation patterns in terms of phasing is less clear. Here we studied adaptation of muscle activity phasing to the relative angular positions of limbs using a split-crank ergometer, where the cranks could be decoupled to allow different spatial angular position relationships. Twenty neurologically healthy individuals performed the specified pedaling tasks at different relative angular positions while surface electromyographic (EMG) signals were recorded bilaterally from eight lower extremity muscles. During each experiment, the relative angular crank positions were altered by increasing or decreasing their difference by randomly ordered increments of 30° over the complete cycle [0° (in phase pedaling); 30, 60, 90, 120, 150, and 180° (standard pedaling); and 210, 240, 270, 300, and 330° out of phase pedaling]. We found that manipulating the relative angular positions of limbs in a pedaling task caused muscle activity phasing changes that were either delayed or advanced, dependent on the relative spatial position of the two cranks and this relationship is well-explained by a sine curve. Further, we observed that the magnitude of phasing changes in biarticular muscles (like rectus femoris) was significantly greater than those of uniarticular muscles (like vastus medialis). These results are important because they provide new evidence that muscle phasing can be systematically influenced by interlimb pathways.

Differential Activation of Projection Neurons by Two Sensory Pathways Contributes to Motor Pattern Selection

Hedrich, U. B. S., Smarandache, C. R., Stein, W. — Wed, 04 Nov 2009 11:06:51 PST

Sensorimotor integration is known to occur at the level of motor circuits as well as in upstream interneurons that regulate motor activity. Here we show, using the crab stomatogastric nervous system (STNS) as a model, that different sensory systems affect the same set of projection neurons. However, they have qualitatively different effects on their activities (excitation vs. inhibition), and these differences contribute to the selection of motor patterns from multifunctional circuits. We compare the actions of the proprioceptive anterior gastric receptor (AGR) and the inferior ventricular (IV) neurons, which relay chemosensory information from the brain to the STNS, on modulatory commissural neurons 1 and 5 (MCN1 and MCN5) and commissural projection neuron 2 (CPN2) and their resulting actions on the gastric mill central pattern generating circuit in the stomatogastric ganglion. When stimulated, AGR and the IV neurons affect all three projection neurons but elicit distinct gastric mill rhythms. The effects of both sensory pathways on the projection neurons differ in the type of excitation provided to CPN2 and MCN5 (electrical vs. chemical) and the effect on MCN1 (direct inhibition by AGR vs. polysynaptic excitation by the IV neurons). The latter is functionally important because a restoration of MCN1 activity during the AGR rhythm made it more similar to that elicited by IV neuron stimulation. Our results thus support the hypothesis that sensory pathways activate different combinations of projection neurons to select distinct outputs from the same neuronal circuit.

Maintenance of Thalamic Epileptiform Activity Depends on the Astrocytic Glutamate-Glutamine Cycle

Bryant, A. S., Li, B., Beenhakker, M. P., Huguenard, J. R. — Wed, 04 Nov 2009 11:06:52 PST

The generation of prolonged neuronal activity depends on the maintenance of synaptic neurotransmitter pools. The astrocytic glutamate-glutamine cycle is a major mechanism for recycling the neurotransmitters GABA and glutamate. Here we tested the effect of disrupting the glutamate-glutamine cycle on two types of neuronal activity patterns in the thalamus: sleep-related spindles and epileptiform oscillations. In recording conditions believed to induce glutamine scarcity, epileptiform oscillations showed a progressive reduction in duration that was partially reversible by the application of exogenous glutamine (300 µM). Blocking uptake of glutamine into neurons with -(methylamino) isobutyric acid (5 mM) caused a similar reduction in oscillation duration, as did blocking neuronal GABA synthesis with 3-mercaptoproprionic acid (10 µM). However, comparable manipulations did not affect sleep spindles. Together, these results support a crucial role for the glutamate-glutamine cycle in providing the neurotransmitters necessary for the generation of epileptiform activity and suggest potential therapeutic approaches that selectively reduce seizure activity but maintain normal neuronal activity.

Multicomponent Control Strategy Underlying Production of Maximal Hand Velocity During Horizontal Arm Swing

Kim, Y.-K., Hinrichs, R. N., Dounskaia, N. — Wed, 04 Nov 2009 11:06:52 PST

Movement control responsible for generation of maximal hand velocity was studied on the example of horizontal arm swing that is a component of various sports activities. The movement was performed with the nondominant arm in similarity with the baseball bat swing. The task was to generate maximum hand velocity at a target. The movement included trunk long-axis rotation and horizontal shoulder and elbow extension. Kinematics and torque analyses were performed to study the organization of fastest movements and to compare trials representing the best and worst performance in each subject. Results revealed complex control strategy, with the trunk, shoulder, and elbow playing unique roles in generation of maximal hand velocity. The trunk provided a crucial contribution, directly, rotating the entire arm, and indirectly, exerting interaction torque that caused swift elbow extension. The major role of the shoulder was to transfer the mechanical effect of trunk motion to the elbow. However, the shoulder became the primary motion generator when the trunk reached its limits of rotation, revealing sequential organization of control. The role of the elbow was to maximally comply with passive influence of proximal joints. The findings are discussed in light of the leading joint hypothesis that offers a straightforward interpretation of control of horizontal arm swing as well as practically efficient recommendations for increases in movement speed. The revealed role of intersegmental dynamics in production of high movement speed suggests that movement slowness characteristic for some motor disorders may be partially a compensatory strategy that facilitates regulation of interaction torque.

Area Summation in Human Visual System: Psychophysics, fMRI, and Modeling

Nurminen, L., Kilpelainen, M., Laurinen, P., Vanni, S. — Wed, 04 Nov 2009 11:06:52 PST

Contextual modulation is a fundamental feature of sensory processing, both on perceptual and on single-neuron level. When the diameter of a visual stimulus is increased, the firing rate of a cell typically first increases (summation field) and then decreases (surround field). Such an area summation function draws a comprehensive profile of the receptive field structure of a neuron, including areas outside the classical receptive field. We investigated area summation in human vision with psychophysics and functional magnetic resonance imaging (fMRI). The stimuli were similar to those used drifting sine wave gratings in previous macaque single-cell area summation studies. A model was developed to facilitate comparison of area summation in fMRI to area summation in psychophysics and single cells. The model consisted of units with an antagonistic receptive field structure found in single cells in the primary visual cortex. The receptive field centers of the model neurons were distributed in the region of the visual field covered by a single voxel. The measured area summation functions were qualitatively similar to earlier single-cell data. The model with parameters derived from psychophysics captured the spatial structure of the summation field in the primary visual cortex as measured with fMRI. The model also generalized to a novel situation in which the neural population was displaced from the stimulus center. The current study shows that contextual modulation arises from similar spatially antagonistic and overlapping excitatory and inhibitory mechanisms, both in single cells and in human vision.

Postural Feedback Scaling Deficits in Parkinson's Disease

Kim, S., Horak, F. B., Carlson-Kuhta, P., Park, S. — Wed, 04 Nov 2009 11:06:52 PST

Many differences in postural responses have been associated with age and Parkinson's disease (PD), but until now there has been no quantitative model to explain these differences. We developed a feedback control model of body dynamics that could reproduce the postural responses of young subjects, elderly subjects, and subjects with PD, and we investigated whether the postural impairments of subjects with PD can be described as an abnormal scaling of postural feedback gain. Feedback gains quantify how the nervous system generates compensatory joint torques based on kinematic responses. Seven subjects in each group experienced forward postural perturbations to seven different backward support surface translations ranging from 3- to 15-cm amplitudes and with a constant duration of 275 ms. Ground reaction forces and joint kinematics were measured to obtain joint torques from inverse dynamics. A full-state feedback controller with a two-segment body dynamic model was used to simulate joint kinematics and kinetics in response to perturbations. Results showed that all three subject groups gradually scaled postural feedback gains as a function of perturbation amplitudes, and the scaling started even before the maximum allowable ankle torque was reached. This result implies that the nervous system takes body dynamics into account and adjusts postural feedback gains to accommodate biomechanical constraints. PD subjects showed significantly smaller than normal ankle feedback gain with low scaling and larger hip feedback gain, which led to an early violation of the flat-foot constraint and unusually small (bradykinetic) postural responses. Our postural feedback control model quantitatively described the postural abnormality of the patients with PD as abnormal feedback gains and reduced ability to modify postural feedback gain with changes in postural challenge.

Adaptation to Visuomotor Rotation Through Interaction Between Posterior Parietal and Motor Cortical Areas

Tanaka, H., Sejnowski, T. J., Krakauer, J. W. — Wed, 04 Nov 2009 11:06:52 PST

Studying how motor adaptation to visuomotor rotation for one reach direction generalizes to other reach directions can provide insight into how visuomotor maps are represented and learned in the brain. Previous psychophysical studies have concluded that postadaptation generalization is restricted to a narrow range of directions around the training direction. A population-coding model that updates the weights between narrow Gaussian-tuned visual units and motor units on each trial reproduced experimental trial-by-trial learning curves for rotation adaptation and the generalization function measured postadaptation. These results suggest that the neurons involved in rotation adaptation have a relatively narrow directional tuning width (~23°). Population coding models with units having broader tuning functions (such as cosine tuning in motor cortex and Gaussian sum in the cerebellum) could not reproduce the narrow single-peaked generalization pattern. Visually selective neurons with narrow Gaussian tuning curves have been identified in posterior parietal cortex, making it a possible site of adaptation to visuomotor rotation. We propose that rotation adaptation proceeds through changes in synaptic weights between neurons in posterior parietal cortex and motor cortex driven by a prediction error computed by the cerebellum.

Substantia Nigra Output to Prefrontal Cortex Via Thalamus in Monkeys. I. Electrophysiological Identification of Thalamic Relay Neurons

Tanibuchi, I., Kitano, H., Jinnai, K. — Wed, 04 Nov 2009 11:06:52 PST

A few studies have been performed in primate basal ganglia–thalamo–prefrontal pathways. Nevertheless, their electrophysiological properties and anatomical arrangements remain obscure. This study examined them in nigro-thalamo-cortical pathways from the substantia nigra pars reticulata (SNr) to the frontal cortex (FRC) via the mediodorsal (MD) and ventral anterior (VA) thalamus in monkeys. First, single thalamocortical neurons with SNr input were identified by antidromic responses to FRC stimulation and by inhibitory orthodromic responses with short latencies (<5 ms) to SNr stimulation. Second, single nigrothalamic neurons were found by antidromic responses to stimulation of the portions of the MD and VA where the thalamocortical neurons were recorded. The inhibitory orthodromic responses in the thalamocortical neurons were considered to be monosynaptically induced by nigral stimulation because the latency distribution of the orthodromic responses in the thalamocortical neurons was similar to that of the antidromic responses in the nigrothalamic neurons. Almost all relay neurons in the rostrolateral MD received inhibitory afferents from the caudolateral SNr and projected to the prefrontal area ventral to the principal sulcus, which constituted the densest nigro-thalamo-cortical projections. Meanwhile, neurons in the VA received inhibitory signals from the whole rostrocaudal extent of the SNr and projected to wide regions of the FRC; neurons in its pars magnocellularis mostly projected to different prefrontal areas, while those in its pars parvocellularis projected to motor areas. This report substantiated the topography of thalamocortical neurons monosynaptically receiving inhibitory SNr input and projecting to the FRC in the primate MD and VA at the single-neuron level.

Substantia Nigra Output to Prefrontal Cortex Via Thalamus in Monkeys. II. Activity of Thalamic Relay Neurons in Delayed Conditional Go/No-Go Discrimination Task

Tanibuchi, I., Kitano, H., Jinnai, K. — Wed, 04 Nov 2009 11:06:52 PST

The present report investigated the involvement of primate nigro-thalamo-cortical projections in discrimination of visual signals with behavioral meaning. We tested the extracellular unit activity of mediodorsal (MD) and ventral anterior (VA) thalamic neurons monosynaptically receiving inhibitory input from the substantia nigra pars reticulata (SNr) and projecting to the frontal cortex in Japanese monkeys performing a delayed conditional go/no-go discrimination task. In the task two colored stimuli (S1, S2) intervened by delay period required the monkeys lifting a lever (go) or not (no-go); the same and different colored pairs of S1 and S2 meant go and no-go signals, respectively. Prominent task-relevant responses were sustained activity with color preference to S1 during delay period and S2-related activity with different firing rates between go and no-go trials. In particular, a high proportion of such go/no-go differential S2-related activity was found in thalamic relay neurons, receiving input from the caudolateral SNr and projecting to the prefrontal area (PSv) ventral to the principal sulcus, in the rostrolateral MD. The findings suggest that the caudolateral SNr–rostrolateral MD–PSv pathways may be possible conduits of signals coding the behavioral meaning of the visual stimuli and thus may be responsible for generating similar neuronal activity in the PSv.

Experience-Dependent Intrinsic Plasticity in Interneurons of Barrel Cortex Layer IV

Sun, Q.-Q. — Wed, 04 Nov 2009 11:06:52 PST

It is unclear whether intrinsic excitabilities of specific interneurons are modulated by sensory experiences. Here, I examined the intrinsic excitabilities of interneurons in "sensory-spared" and "sensory-deprived" cortices of GAD67-GFP mice. The results showed that whisker trimming, begun at postnatal day 7 for 3 wk, induced significant changes in intrinsic and firing properties of fast-spiking (FS) but not regular spiking nonpyramidal (RSNP) cells. Firing threshold, spike frequency, spike adaptation index, and input resistance of FS cells were significantly altered by sensory deprivation such that FS cells became less excitable. An up-regulation of IA currents in FS cells appeared to be responsible. Along with changes in the intrinsic properties of FS cells, whisker trimming also induced a robust reduction in the number of vesicular glutamate transporter 2 positive varicosities and parvalbumin expression and the strength of thalamocortical (TC) excitatory postsynaptic currents in FS cells in the "sensory-deprived barrels." The probability of spike induction by TC stimulus was reduced by 30% and the spike jitter was increased in sensory-deprived FS cells. These results suggest that the FS networks are selectively inhibited by sensory deprivation. The concurrent changes of intrinsic properties and expression of parvalbumin in FS but not RSNP cells with TC synapses support a contribution from the TC pathway and glutamate to sensory-induced activity-dependent intrinsic plasticity of inhibitory networks in barrel cortex.

Radial Biases in the Processing of Motion and Motion-Defined Contours by Human Visual Cortex

Clifford, C. W. G., Mannion, D. J., McDonald, J. S. — Wed, 04 Nov 2009 11:06:52 PST

Luminance gratings reportedly produce a stronger functional magnetic resonance imaging (fMRI) blood oxygen level–dependent (BOLD) signal in those parts of the retinotopic cortical maps where they are oriented radially to the point of fixation. We sought to extend this finding by examining anisotropies in the response of cortical areas V1–V3 to motion-defined contour stimuli. fMRI at 3 Tesla was used to measure the BOLD signal in the visual cortex of six human subjects. Stimuli were composed of strips of spatial white noise texture presented in an annular window. The texture in alternate strips moved in opposite directions (left–right or up–down). The strips themselves were static and tilted 45° left or right from vertical. Comparison with maps of the visual field obtained from phase-encoded retinotopic analysis revealed systematic patterns of radial bias. For motion, a stronger response to horizontal was evident within V1 and along the borders between V2 and V3. For orientation, the response to leftward tilted contours was greater in left dorsal and right ventral V1–V3. Radial bias for the orientation of motion-defined contours analogous to that reported previously for luminance gratings could reflect cue-invariant processing or the operation of distinct mechanisms subject to similar anisotropies in orientation tuning. Radial bias for motion might be related to the phenomenon of "motion streaks," whereby temporal integration by the visual system introduces oriented blur along the axis of motion. We speculate that the observed forms of radial bias reflect a common underlying anisotropy in the representation of spatiotemporal image structure across the visual field.

Direct Activation and Temporal Response Properties of Rabbit Retinal Ganglion Cells Following Subretinal Stimulation

Tsai, D., Morley, J. W., Suaning, G. J., Lovell, N. H. — Wed, 04 Nov 2009 11:06:52 PST

In the last decade several groups have been developing vision prostheses to restore visual perception to the profoundly blind. Despite some promising results from human trials, further understanding of the neural mechanisms involved is crucial for improving the efficacy of these devices. One of the techniques involves placing stimulating electrodes in the subretinal space between the photoreceptor layer and the pigment epithelium to evoke neural responses in the degenerative retina. This study used cell-attached and whole cell current-clamp recordings to investigate the responses of rabbit retinal ganglion cells (RGCs) following subretinal stimulation with 25-µm-diameter electrodes. We found that direct RGC responses with short latency (≤2 ms using 0.1-ms pulses) could be reliably elicited. The thresholds for these responses were reported for on, off, and on–off RGCs over pulse widths 0.1–5.0 ms. During repetitive stimulation these direct activation responses were more readily elicited than responses arising from stimulation of the retinal network. The temporal spiking characteristics of RGCs were characterized as a function of stimulus configurations. We found that the response profiles could be generalized into four classes with distinctive properties. Our results suggest that for subretinal vision prostheses short pulses are preferable for efficacy and safety considerations, and that direct activation of RGCs will be necessary for reliable activation during high-frequency stimulation.

Functional Asymmetries Revealed in Visually Guided Saccades: An fMRI Study

Wed, 04 Nov 2009 11:06:52 PST

Because eye movements are a fundamental tool for spatial exploration, we hypothesized that the neural bases of these movements in humans should be under right cerebral dominance, as already described for spatial attention. We used functional magnetic resonance imaging in 27 right-handed participants who alternated central fixation with either large or small visually guided saccades (VGS), equally performed in both directions. Hemispheric functional asymmetry was analyzed to identify whether brain regions showing VGS activation elicited hemispheric asymmetries. Hemispheric anatomical asymmetry was also estimated to assess its influence on the VGS functional lateralization. Right asymmetrical activations of a saccadic/attentional system were observed in the lateral frontal eye fields (FEF), the anterior part of the intraparietal sulcus (aIPS), the posterior third of the superior temporal sulcus (STS), the occipitotemporal junction (MT/V5 area), the middle occipital gyrus, and medially along the calcarine fissure (V1). The present rightward functional asymmetries were not related to differences in gray matter (GM) density/sulci positions between right and left hemispheres in the precentral, intraparietal, superior temporal, and extrastriate regions. Only V1 asymmetries were explained for almost 20% of the variance by a difference in the position of the right and left calcarine fissures. Left asymmetrical activations of a saccadic motor system were observed in the medial FEF and in the motor strip eye field along the Rolando sulcus. They were not explained by GM asymmetries. We suggest that the leftward saccadic motor asymmetry is part of a general dominance of the left motor cortex in right-handers, which must include an effect of sighting dominance. Our results demonstrate that, although bilateral by nature, the brain network involved in the execution of VGSs, irrespective of their direction, presented specific right and left asymmetries that were not related to anatomical differences in sulci positions.

Long-Latency Responses During Reaching Account for the Mechanical Interaction Between the Shoulder and Elbow Joints

Kurtzer, I., Pruszynski, J. A., Scott, S. H. — Wed, 04 Nov 2009 11:06:52 PST

Although considerable research indicates that reaching movements rely on knowledge of the arm's mechanical properties and environment to anticipate and counter predictable loads, far less research has examined whether this degree of sophistication is present for on-line corrections during reaching. Here we examine the R2/3 response to mechanical perturbations (45–100 ms, also called the long-latency reflex), which is highly flexible and includes the fastest possible contribution from primary motor cortex, a key neural substrate for self-initiated action. Torque perturbations were occasionally and unexpectedly applied to the subject's shoulder and/or elbow in the course of performing reaching movements. Critically, these perturbations would evoke different patterns of feedback corrections from a shoulder extensor muscle if it countered only the local shoulder displacement relative to unperturbed motion or accounted for the mechanical interactions between the shoulder and elbow joints and countered the underlying shoulder torque. Our results show that the earliest response (R1: 20–45 ms) reflected local shoulder displacement, whereas the R2/3 response (45–100 ms) reflected knowledge of multijoint dynamics. Moreover, the same pattern of feedback occurred whether the shoulder muscle helped initiate the movement (during its agonist phase) or helped terminate the movement (during its antagonist phase). These results contribute to the accumulating evidence that highly sophisticated feedback control underlies motor behavior and are consistent with a shared neural substrate, such as primary motor cortex, for feedforward and feedback control.

Type of Featural Attention Differentially Modulates hMT+ Responses to Illusory Motion Aftereffects

Wed, 04 Nov 2009 11:06:52 PST

Activity in the human motion complex (hMT⁺/V5) is related to the perception of motion, be it either real surface motion or an illusion of motion such as apparent motion (AM) or motion aftereffect (MAE). It is a long-lasting debate whether illusory motion-related activations in hMT⁺ represent the motion itself or attention to it. We have asked whether hMT⁺ responses to MAEs are present when shifts in arousal are suppressed and attention is focused on concurrent motion versus nonmotion features. Significant enhancement of hMT⁺ activity was observed during MAEs when attention was focused either on concurrent spatial angle or color features. This observation was confirmed by direct comparison of adapting (MAE inducing) versus nonadapting conditions. In contrast, this effect was diminished when subjects had to report on concomitant speed changes of superimposed AM. The same finding was observed for concomitant orthogonal real motion (RM), suggesting that selective attention to concurrent illusory or real motion was interfering with the saliency of MAE signals in hMT⁺. We conclude that MAE-related changes in the global activity of hMT⁺ are present provided selective attention is not focused on an interfering feature such as concurrent motion. Accordingly, there is a genuine MAE-related motion signal in hMT⁺ that is neither explained by shifts in arousal nor by selective attention.

Transient Firing of Dorsal Raphe Neurons Encodes Diverse and Specific Sensory, Motor, and Reward Events

Ranade, S. P., Mainen, Z. F. — Wed, 04 Nov 2009 11:06:52 PST

Serotonin (5-hydroxytryptamine [5-HT]) is known to influence a wide range of behaviors and physiological processes, but relatively little is known about events that trigger 5-HT release. To address this issue, we recorded from neurons in the dorsal raphe nucleus (DRN) in rats performing an odor-guided spatial decision task. A large fraction of DRN neurons showed transient firing time locked to behavioral events on timescales as little as 20 ms. DRN transients were sometimes correlated with reward parameters, but also encoded specific sensorimotor events, including stimulus identity and response direction. These behavioral correlates were diverse but showed no apparent relationship with waveform or other firing properties indicative of neurochemical identity. These results suggest that the 5-HT system does not encode a unitary signal and that it will broadcast specific information to the forebrain with speed and precision sufficient not only to modulate but also to dynamically sculpt ongoing information processing.

Excitatory and Inhibitory Synapses in Neuropeptide Y-Expressing Striatal Interneurons

Wed, 04 Nov 2009 11:06:52 PST

Although rare, interneurons are pivotal in governing striatal output by extensive axonal arborizations synapsing on medium spiny neurons. Using a genetically modified mouse strain in which a green fluorescent protein (GFP) is driven to be expressed under control of the neuropeptide Y (NPY) promoter, we identified NPY interneurons and compared them with striatal principal neurons. We found that the bacteria artificial chromosome (BAC)-npy mouse expresses GFP with high fidelity in the striatum to the endogenous expression of NPY. Patch-clamp analysis from NPY neurons showed a heterogeneous population of striatal interneurons. In the majority of cells, we observed spontaneous firing of action potentials in extracellular recordings. On membrane rupture, most NPY interneurons could be classified as low-threshold spiking interneurons and had high-input resistance. Voltage-clamp recordings showed that both GABA and glutamate gated ion channels mediate synaptic inputs onto these striatal interneurons. AMPA receptor–mediated spontaneous excitatory postsynaptic currents (sEPSCs) were small in amplitude and infrequent in NPY neurons. Evoked EPSCs did not show short-term plasticity but some rectification. Evoked N-methyl-d-aspartate (NMDA) EPSCs had fast decay kinetics and were poorly sensitive to an NR2B subunit containing NMDA receptor blocker. Spontaneous inhibitory postsynaptic currents (sIPSCs) were mediated by GABA_A receptors and were quite similar among all striatal neurons studied. On the contrary, evoked IPSCs decayed faster in NPY neurons than in other striatal neurons. These data report for the first time specific properties of synaptic transmission to NPY striatal interneurons.

EEG Generator--A Model of Potentials in a Volume Conductor

Avitan, L., Teicher, M., Abeles, M. — Wed, 04 Nov 2009 11:06:52 PST

EEG generator—a model of potentials in a volume conductor. The potential recorded over the cortex electro-corticogram (ECoG) or over the scalp [electroencephalograph (EEG)] derives from the activity of many sources known as "EEG generators." The recorded amplitude is basically a function of the unitary potential of a generator and the statistical relationship between different EEG generators in the recorded population. In this study, we first suggest a new definition of the EEG generator. We use the theory of potentials in a volume conductor and model the contribution of a single synapse activated to the surface potential. We then model the contribution of the generator to the surface potential. Once the generator and its contribution are well defined, we can quantitatively assess the degree of synchronization among generators. The measures obtained by the model for a real life scenario of a group of generators organized in a specific statistical way were consistent with the expected values that were reported experimentally. The study sheds new light on macroscopic modeling approaches which make use of mean soma membrane potential. We showed major contribution of activity of superficial apical synapses to the ECoG signal recorded relative to lower somatic or basal synapses activity.

Characterizing Learning by Simultaneous Analysis of Continuous and Binary Measures of Performance

Wed, 04 Nov 2009 11:06:52 PST

Continuous observations, such as reaction and run times, and binary observations, such as correct/incorrect responses, are recorded routinely in behavioral learning experiments. Although both types of performance measures are often recorded simultaneously, the two have not been used in combination to evaluate learning. We present a state-space model of learning in which the observation process has simultaneously recorded continuous and binary measures of performance. We use these performance measures simultaneously to estimate the model parameters and the unobserved cognitive state process by maximum likelihood using an approximate expectation maximization (EM) algorithm. We introduce the concept of a reaction-time curve and reformulate our previous definitions of the learning curve, the ideal observer curve, the learning trial and between-trial comparisons of performance in terms of the new model. We illustrate the properties of the new model in an analysis of a simulated learning experiment. In the simulated data analysis, simultaneous use of the two measures of performance provided more credible and accurate estimates of the learning than either measure analyzed separately. We also analyze two actual learning experiments in which the performance of rats and of monkeys was tracked across trials by simultaneously recorded reaction and run times and the correct and incorrect responses. In the analysis of the actual experiments, our algorithm gave a straightforward, efficient way to characterize learning by combining continuous and binary measures of performance. This analysis paradigm has implications for characterizing learning and for the more general problem of combining different data types to characterize the properties of a neural system.

Are There Nociceptive-Specific Brain Potentials?

Baumgartner, U., Treede, R.-D. — Wed, 04 Nov 2009 11:06:52 PST

Are There Nociceptive-Specific Brain Potentials? Reply to Baumgartner and Treede

Mouraux, A., Plaghki, L., Iannetti, G. D. — Wed, 04 Nov 2009 11:06:52 PST

Corrigendum

Wed, 04 Nov 2009 11:06:52 PST

Presynaptic Mechanisms of Endocannabinoid-Mediated Long-Term Depression in the Hippocampus

Lafourcade, C. A. — Mon, 19 Oct 2009 09:34:40 PDT

Endogenous cannabinoids (eCBs) mobilized from postsynaptic cells activate presynaptic cannabinoid receptors and thereby inhibit synaptic transmitter release. The inhibition can be either brief (seconds) or long-lasting (minutes to hours). Recent studies provide insight into the presynaptic mechanisms responsible for long-lasting, eCB-mediated long-term depression. Among these, the proteins PKA and RIM1 appear to be crucial, although other possibilities are emerging.

Spatial and Temporal Integration of Visual Motion Signals for Smooth Pursuit Eye Movements in Monkeys

Osborne, L. C., Lisberger, S. G. — Mon, 19 Oct 2009 09:34:40 PDT

To probe how the brain integrates visual motion signals to guide behavior, we analyzed the smooth pursuit eye movements evoked by target motion with a stochastic component. When each dot of a texture executed an independent random walk such that speed or direction varied across the spatial extent of the target, pursuit variance increased as a function of the variance of visual pattern motion. Noise in either target direction or speed increased the variance of both eye speed and direction, implying a common neural noise source for estimating target speed and direction. Spatial averaging was inefficient for targets with >20 dots. Together these data suggest that pursuit performance is limited by the properties of spatial averaging across a noisy population of sensory neurons rather than across the physical stimulus. When targets executed a spatially uniform random walk in time around a central direction of motion, an optimized linear filter that describes the transformation of target motion into eye motion accounted for ~50% of the variance in pursuit. Filters had widths of ~25 ms, much longer than the impulse response of the eye, and filter shape depended on both the range and correlation time of motion signals, suggesting that filters were products of sensory processing. By quantifying the effects of different levels of stimulus noise on pursuit, we have provided rigorous constraints for understanding sensory population decoding. We have shown how temporal and spatial integration of sensory signals converts noisy population responses into precise motor responses.

Origins of Abnormal Excitability in Biceps Brachii Motoneurons of Spastic-Paretic Stroke Survivors

Mottram, C. J., Suresh, N. L., Heckman, C. J., Gorassini, M. A., Rymer, W. Z. — Mon, 19 Oct 2009 09:34:40 PDT

Stroke survivors often exhibit abnormal motoneuron excitability, manifested clinically as spasticity with exaggerated stretch reflexes in resting muscles. We examined whether this abnormal excitability is a result of increased activation of intrinsic voltage-dependent persistent inward currents (PICs) or whether it is a result of enhanced synaptic inputs to the motoneuron. This distinction was made by recording firing rate profiles of pairs of motor units during isometric contractions of elbow flexor muscles. To estimate PIC amplitude, the discharge of the lower-threshold (reporter) motor unit of the pair was used to estimate the synaptic input to the higher-threshold (test) motor unit. The estimated synaptic input required to recruit the test unit was compared with the synaptic input when the test unit was derecruited (F) and this served as an estimate of the intrinsic (PIC) contribution to motoneuron firing. We found that PIC estimates were not larger in spastic-paretic motoneurons (F = 4.0 ± 1.6 pps) compared with contralateral (4.6 ± 1.4 pps) and age-matched healthy control motoneurons (3.8 ± 1.7, all P > 0.1). Instead, following the voluntary contractions, the majority of lower-threshold motor units in spastic-paretic muscles (83%) exhibited spontaneous discharge, compared with 14% of contralateral and 0% of control motor units. Furthermore, there was strong co-modulation of simultaneously active units in spastic muscle. The presence of ongoing, correlated unit activity at "rest," coupled with firing behavior at recruitment unique to lower-threshold motor units in spastic muscles, suggested that firing changes are likely a result of a low-level depolarizing synaptic drive to the resting motoneuron pool.

Encoding and Decoding of Learned Smooth-Pursuit Eye Movements in the Floccular Complex of the Monkey Cerebellum

Medina, J. F., Lisberger, S. G. — Mon, 19 Oct 2009 09:34:40 PDT

We recorded the simple-spike (SS) firing of Purkinje cells (PCs) in the floccular complex both during normal pursuit caused by step-ramp target motions and after learning induced by a consistently timed change in the direction of target motion. The encoding of eye movement by the SS firing rate of individual PCs was described by a linear regression model, in which the firing rate is a sum of weighted components related to eye acceleration, velocity, and position. Although the model fit the data well for individual conditions, the regression coefficients for the learned component of firing often differed substantially from those for normal pursuit of step-ramp target motion. We suggest that the different encoding of learned versus normal pursuit responses in individual PCs reflects different amounts of learning in their inputs. The decoded output from the floccular complex, estimated by averaging responses across the population of PCs, also was fitted by the regression model. Regression coefficients were equal for the two conditions for on-direction pursuit, but differed for off-direction target motion. We conclude that the average output from the population of floccular PCs provides some, but not all, of the neural signals that drive the learned component of pursuit and that plasticity outside of the flocculus makes an important contribution.

Neural Correlates of Novel Object and Novel Location Recognition Behavior in the Mouse Anterior Cingulate Cortex

Weible, A. P., Rowland, D. C., Pang, R., Kentros, C. — Mon, 19 Oct 2009 09:34:40 PDT

The anterior cingulate cortex (ACC) is a component of the limbic system implicated in a wide variety of functions spanning motor and sensory information processing, memory, attention, novelty detection, and comparisons of expectation versus outcome. It remains unclear how much of this functional diversity stems from differences in methodology or interpretation versus truly reflecting the range of processes in which the ACC is involved. In the present study, ACC neuronal activity was examined in freely behaving mice (C57BL6/J) under conditions allowing investigation of many of the cited functions in conditions free from externally applied rules: tests of novel object and novel location recognition memory. Behavioral activity and neuronal activity were recorded first in the open field, during the initial exposure and subsequent familiarization to two identical objects, and finally during the recognition memory tests. No discernible stable firing correlates of ACC neurons were found in the open field, but the addition of objects led to lasting changes in the firing patterns of many ACC neurons around one or both of the object locations. During the novel location test, some neurons followed the familiar object to its new location, others fired exclusively where the object had been, and yet others fired to both current and former object locations. Many of these same features were observed during tests of object recognition memory. However, the magnitude of the neuronal preference for the novel or the familiar object was markedly greater than that observed during either the tests of location recognition or novel object preferences in animals that did not exhibit the expected behavior. The present study reveals, for the first time, single-neuron correlates of object and location recognition behaviors in the rodent ACC and suggests that neurons of the ACC provide a distributed representation of all of the salient features of a task.

Comparison of Spatial Summation Properties of Neurons in Macaque V1 and V2

Shushruth, S., Ichida, J. M., Levitt, J. B., Angelucci, A. — Mon, 19 Oct 2009 09:34:41 PDT

In visual cortex, responses to stimulation of the receptive field (RF) are modulated by simultaneous stimulation of the RF surround. The mechanisms for surround modulation remain unidentified. We previously proposed that in the primary visual cortex (V1), near surround modulation is mediated by geniculocortical and horizontal connections and far surround modulation by interareal feedback connections. To understand spatial integration in the secondary visual cortex (V2) and its underlying circuitry, we have characterized spatial summation in different V2 layers and stripe compartments and compared it to that in V1. We used grating stimuli in circular and annular apertures of different sizes to estimate the extent and sensitivity of RF and surround components in V1 and V2. V2 RFs and surrounds were twice as large as those in V1. As in V1, V2 RFs doubled in size when measured at low contrast. In both V1 and V2, surrounds were about fivefold the size of the RF and the far surround could exceed 12.5° in radius, averaging 5.5° in V1 and 9.2° in V2. The strength of surround suppression was similar in both areas. Thus although differing in spatial scale, the interactions among RF components are similar in V1 and V2, suggesting similar underlying mechanisms. As in V1, the extent of V2 horizontal connections matches that of the RF center, but is much smaller than the largest far surrounds, which likely derive from interareal feedback. In V2, we found no laminar or stripe differences in size and magnitude of surround suppression, suggesting conservation across stripes of the basic circuit for surround modulation.

Simultaneous Preparation of Multiple Potential Movements: Opposing Effects of Spatial Proximity Mediated by Premotor and Parietal Cortex

Praamstra, P., Kourtis, D., Nazarpour, K. — Mon, 19 Oct 2009 09:34:41 PDT

Neurophysiological studies in monkey have suggested that premotor and motor cortex may prepare for multiple movements simultaneously, sustained by cooperative and competitive interactions within and between the neural populations encoding different actions. Here, we investigate whether competition between alternative movement directions, manipulated in terms of number and spatial angle, is reflected in electroencephalographic (EEG) measures of (pre)motor cortical activity in humans. EEG was recorded during performance of a center-out pointing task in which response signals were preceded by cues providing prior information in the form of arrows pointing to one or more possible movement targets. Delay-period activity in (pre)motor cortex was modulated in the predicted manner by the number of possible movement directions and by the angle separating them. Response latencies, however, were determined not only by the amplitude of movement-preparatory activity, but also by differences in the duration of stimulus evaluation against the visuospatial memory of the cue, reflected in EEG potentials originating from posterior parietal cortex (PPC). Specifically, the spatial proximity of possible movement targets was processed differently by (pre)motor and posterior parietal cortex. Spatial proximity enhanced the amplitude of (pre)motor cortex preparatory activity during the delay period but delayed evaluation of the response signal in the PPC, thus producing opposite effects on response latency. The latter finding supports distributed control of movement decisions in the frontoparietal network, revealing a feature of distributed control that is of potential significance for the understanding of distracter effects in reaching and pointing.

Breakdown of Effective Connectivity During Slow Wave Sleep: Investigating the Mechanism Underlying a Cortical Gate Using Large-Scale Modeling

Esser, S. K., Hill, S., Tononi, G. — Mon, 19 Oct 2009 09:34:41 PDT

Effective connectivity between cortical areas decreases during slow wave sleep. This decline can be observed in the reduced interareal propagation of activity evoked either directly in cortex by transcranial magnetic stimulation (TMS) or by sensory stimulation. We present here a large-scale model of the thalamocortical system that is capable of reproducing these experimental observations. This model was constructed according to a large number of physiological and anatomical constraints and includes over 30,000 spiking neurons interconnected by more than 5 million synaptic connections and organized into three cortical areas. By simulating the different effects of arousal promoting neuromodulators, the model can produce a waking or a slow wave sleep-like mode. In this work, we also seek to explain why intercortical signal transmission decreases in slow wave sleep. The traditional explanation for reduced brain responses during this state, a thalamic gate, cannot account for the reduced propagation between cortical areas. Therefore we propose that a cortical gate is responsible for this diminished intercortical propagation. We used our model to test three candidate mechanisms that might produce a cortical gate during slow wave sleep: a propensity to enter a local down state following perturbation, which blocks the propagation of activity to other areas, increases in potassium channel conductance that reduce neuronal responsiveness, and a shift in the balance of synaptic excitation and inhibition toward inhibition, which decreases network responses to perturbation. Of these mechanisms, we find that only a shift in the balance of synaptic excitation and inhibition can account for the observed in vivo response to direct cortical perturbation as well as many features of spontaneous sleep.

Visual Cues Signaling Object Grasp Reduce Interference in Motor Learning

Cothros, N., Wong, J., Gribble, P. L. — Mon, 19 Oct 2009 09:34:41 PDT

Recent motor learning studies show that human subjects and nonhuman primates form neural representations of novel mechanical environments and associated forces. Whereas proficient adaptation is seen for a single force field, when faced with multiple novel force environments, movement performance and in particular the ability to switch between different force environments declines. It is difficult to reconcile these findings with the notion that primates can proficiently switch between multiple motor skills. Conceivably, particular kinds of sensory, cognitive, or perceptual contextual cues are required. This study examined the effect of visual feedback on motor learning, in particular, cues that simulated interaction with a virtual object. A robot arm was used to deliver novel patterns of forces (force fields) to the limb during reaching movements. We tested the possibility that subjects transition more easily between novel forces and their sudden absence when they are accompanied by visual cues that relate to object grasp. We used a virtual display system to present subjects with different kinds of visual feedback during reaching, including illusory feedback, indicating grasp of a virtual object during reaching in the force field, and object release in the absence of forces. Throughout the experiment, subjects in fact maintained grasp of the robot. We found that, indeed, the most effective visual cues were those associating the force field with grasp of the virtual object and the absence of the force field with release of the object. Our findings show more broadly that specific visual cues can protect motor skills from interference.

Odorant Concentration Dependence in Electroolfactograms Recorded From the Human Olfactory Epithelium

Mon, 19 Oct 2009 09:34:41 PDT

Electroolfactograms (EOGs) are the summated generator potentials of olfactory receptor neurons measured directly from the olfactory epithelium. To validate the sensory origin of the human EOG, we set out to ask whether EOGs measured in humans were odorant concentration dependent. Each of 22 subjects (12 women, mean age = 23.3 yr) was tested with two odorants, either valeric acid and linalool (n = 12) or isovaleric acid and l-carvone (n = 10), each delivered at four concentrations diluted with warm (37°C) and humidified (80%) odorless air. In behavior, increased odorant concentration was associated with increased perceived intensity (all F > 5, all P < 0.001). In EOG, increased odorant concentration was associated with increased area under the EOG curve (all F > 8, all P < 0.001). These findings substantiate EOG as a tool for probing olfactory coding directly at the level of olfactory receptor neurons in humans.

On the Nature of the Intrinsic Connectivity of the Cat Motor Cortex: Evidence for a Recurrent Neural Network Topology

Capaday, C., Ethier, C., Brizzi, L., Sik, A., van Vreeswijk, C., Gingras, D. — Mon, 19 Oct 2009 09:34:41 PDT

The details and functional significance of the intrinsic horizontal connections between neurons in the motor cortex (MCx) remain to be clarified. To further elucidate the nature of this intracortical connectivity pattern, experiments were done on the MCx of three cats. The anterograde tracer biocytin was ejected iontophoretically in layers II, III, and V. Some 30–50 neurons within a radius of ~250 µm were thus stained. The functional output of the motor cortical point at which biocytin was injected, and of the surrounding points, was identified by microstimulation and electromyographic recordings. The axonal arborizations of the stained neurons were traced under camera lucida. The axon collaterals were extensive, reaching distances of ≤7 mm from the injection site. More importantly, the axonal branches were studded all along their course with boutons. The vast majority of boutons formed synaptic contacts on the target cells as identified by electron microscopy. The majority of these boutons made asymmetric (type I, excitatory) synapses mainly on dendritic spines. The bouton density decreased approximately monotonically with distance from the center of the injection. Cluster analysis, lagged covariance analysis, and eigenvalue decomposition showed the bouton distribution map to be unimodal. Superposition of the synaptic bouton distribution map and the motor output map revealed that motor cortical neurons don't make point-to-point connections but rather bind together the representations of a variety of muscles within a large neighborhood. This recurrent-network type connectivity strongly supports the hypothesis that the MCx controls the musculature in an integrated manner.

Stable Encoding of Task Structure Coexists With Flexible Coding of Task Events in Sensorimotor Striatum

Mon, 19 Oct 2009 09:34:41 PDT

The sensorimotor striatum, as part of the brain's habit circuitry, has been suggested to store fixed action values as a result of stimulus-response learning and has been contrasted with a more flexible system that conditionally assigns values to behaviors. The stability of neural activity in the sensorimotor striatum is thought to underlie not only normal habits but also addiction and clinical syndromes characterized by behavioral fixity. By recording in the sensorimotor striatum of mice, we asked whether neuronal activity acquired during procedural learning would be stable even if the sensory stimuli triggering the habitual behavior were altered. Contrary to expectation, both fixed and flexible activity patterns appeared. One, representing the global structure of the acquired behavior, was stable across changes in task cuing. The second, a fine-grain representation of task events, adjusted rapidly. Such dual forms of representation may be critical to allow motor and cognitive flexibility despite habitual performance.

Membrane Capacitance Measurements Revisited: Dependence of Capacitance Value on Measurement Method in Nonisopotential Neurons

Mon, 19 Oct 2009 09:34:41 PDT

During growth or degeneration neuronal surface area can change dramatically. Measurements of membrane protein concentration, as in ion channel or ionic conductance density, are often normalized by membrane capacitance, which is proportional to the surface area, to express changes independently from cell surface variations. Several electrophysiological protocols are used to measure cell capacitance, all based on the assumption of membrane isopotentiality. Yet, most neurons violate this assumption because of their complex anatomical structure, raising the question of which protocol yields measurements that are closest to the actual total membrane capacitance. We measured the capacitance of identified neurons from crab stomatogastric ganglia using three different protocols: the current-clamp step, the voltage-clamp step, and the voltage-clamp ramp protocols. We observed that the current-clamp protocol produced significantly higher capacitance values than those of either voltage-clamp protocol. Computational models of various anatomical complexities suggest that the current-clamp protocol can yield accurate capacitance estimates. In contrast, the voltage-clamp protocol estimates rapidly deteriorate as isopotentiality is reduced. We provide a mathematical description of these results by analyzing a simple two-compartment model neuron to facilitate an intuitive understanding of these methods. Together, the experiments, modeling, and mathematical analysis indicate that accurate total membrane capacitance measurements cannot be obtained with voltage-clamp protocols in nonisopotential neurons. Furthermore, although current-clamp steps can theoretically yield accurate measurements, experimentalists should be aware of limitations imposed by step duration and numerical errors during fitting procedures to obtain the membrane time constant.

Excitation of Mouse Superficial Dorsal Horn Neurons by Histamine and/or PAR-2 Agonist: Potential Role in Itch

Akiyama, T., Carstens, M. I., Carstens, E. — Mon, 19 Oct 2009 09:34:41 PDT

Recent studies have suggested the existence of separate transduction mechanisms and sensory pathways for histamine and nonhistaminergic types of itch. We studied whether histamine and an agonist of the protease-activated receptor (PAR)-2, associated with nonhistaminergic itch, excite murine dorsal horn neurons. Single units were recorded in superficial lumbar dorsal horn of adult ICR mice anesthetized with pentobarbital. Unit activity was searched using a small intradermal hindpaw injection of histamine or the PAR-2 agonist SLIGRL-NH2. Isolated units were subsequently challenged with intradermal histamine followed by SLIGRL-NH2 (each 50 µg/1 µl) or reverse order, followed by mechanical, thermal, and algogenic stimuli. Forty-three units were classified as wide dynamic range (62%), nociceptive specific (22%), or mechano insensitive (16%). Twenty units gave prolonged (mean, 10 min) discharges to intradermal injection of histamine; 76% responded to subsequent SLIGRL-NH2, often more briefly. Units additionally responded to noxious heat (63%), cooling (43%), topical mustard oil (53%), and intradermal capsaicin (67%). Twenty-two other units gave prolonged (mean, 5 min) responses to initial intradermal injection of SLIGRL-NH2; 85% responded to subsequent intradermal histamine. They also responded to noxious heat (75%), mustard oil (93%), capsaicin (63%), and one to cooling. Most superficial dorsal horn neurons were excited by both histamine and the PAR-2 agonist, suggesting overlapping pathways for histamine- and non–histamine-mediated itch. Because the large majority of pruritogen-responsive neurons also responded to noxious stimuli, itch may be signaled at least partly by a population code.

Phrenic Motoneuron Discharge Patterns During Hypoxia-Induced Short-Term Potentiation in Rats

Lee, K.-Z., Reier, P. J., Fuller, D. D. — Mon, 19 Oct 2009 09:34:41 PDT

Hypoxia-induced short-term potentiation (STP) of respiratory motor output is manifested by a progressive increase in activity after the acute hypoxic response and a gradual decrease in activity on termination of hypoxia. We hypothesized that STP would be differentially expressed between physiologically defined phrenic motoneurons (PhrMNs). Phrenic nerve "single fiber" recordings were used to characterize PhrMN discharge in anesthetized, vagotomized and ventilated rats. PhrMNs were classified as early (Early-I) or late inspiratory (Late-I) according to burst onset relative to the contralateral phrenic neurogram during normocapnic baseline conditions. During hypoxia (F_IO₂ = 0.12–0.14, 3 min), both Early-I and Late-I PhrMNs abruptly increased discharge frequency. Both cell types also showed a progressive increase in frequency over the remainder of hypoxia. However, Early-I PhrMNs showed reduced overall discharge duration and total spikes/breath during hypoxia, whereas Late-I PhrMNs maintained constant discharge duration and therefore increased the number of spikes/breath. A population of previously inactive (i.e., silent) PhrMNs was recruited 48 ± 8 s after hypoxia onset. These PhrMNs had a Late-I onset, and the majority (8/9) ceased bursting promptly on termination of hypoxia. In contrast, both Early-I and Late-I PhrMNs showed post-hypoxia STP as reflected by greater discharge frequencies and spikes/breath during the post-hypoxic period (P < 0.01 vs. baseline). We conclude that the expression of phrenic STP during hypoxia reflects increased activity in previously active Early-I and Late-I PhrMNs and recruitment of silent PhrMNs. post-hypoxia STP primarily reflects persistent increases in the discharge of PhrMNs, which were active before hypoxia.

Enhanced Calcium Buffering in F344 Rat Cholinergic Basal Forebrain Neurons Is Associated With Age-Related Cognitive Impairment

Mon, 19 Oct 2009 09:34:41 PDT

Alterations in neuronal Ca²⁺ homeostasis are important determinants of age-related cognitive impairment. We examined the Ca²⁺ influx, buffering, and electrophysiology of basal forebrain neurons in adult, middle-aged, and aged male F344 behaviorally assessed rats. Middle-aged and aged rats were characterized as cognitively impaired or unimpaired by water maze performance relative to young cohorts. Patch-clamp experiments were conducted on neurons acutely dissociated from medial septum/nucleus of the diagonal band with post hoc identification of phenotypic marker mRNA using single-cell RT-PCR. We measured whole cell calcium and barium currents and dissected these currents using pharmacological agents. We combined Ca²⁺ current recording with Ca²⁺-sensitive ratiometric microfluorimetry to measure Ca²⁺ buffering. Additionally, we sought changes in neuronal firing properties using current-clamp recording. There were no age- or cognition-related changes in the amplitudes or fractional compositions of the whole cell Ca²⁺ channel currents. However, Ca²⁺ buffering was significantly enhanced in cholinergic neurons from aged cognitively impaired rats. Moreover, increased Ca²⁺ buffering was present in middle-aged rats that were not cognitively impaired. Firing properties were largely unchanged with age or cognitive status, except for an increase in the slow afterhyperpolarization in aged cholinergic neurons, independent of cognitive status. Furthermore, acutely dissociated basal forebrain neurons in which choline acetyltransferase mRNA was detected had the electrophysiological profiles of identified cholinergic neurons. We conclude that enhanced Ca²⁺ buffering by cholinergic basal forebrain neurons may be important during aging.

Activity-Dependent Modulation of Glutamatergic Signaling in the Developing Rat Dorsal Horn by Early Tissue Injury

Li, J., Walker, S. M., Fitzgerald, M., Baccei, M. L. — Mon, 19 Oct 2009 09:34:41 PDT

Tissue injury in early life can produce distinctive effects on pain processing, but little is known about the underlying neural mechanisms. Neonatal inflammation modulates excitatory synapses in spinal nociceptive circuits, but it is unclear whether this results directly from altered afferent input. Here we investigate excitatory and inhibitory synaptic transmission in the rat superficial dorsal horn following neonatal hindlimb surgical incision using in vitro patch-clamp recordings and test the effect of blocking peripheral nerve activity on the injury-evoked changes. Surgical incision through the skin and muscle of the hindlimb at postnatal day 3 (P3) or P10 selectively increased the frequency, but not amplitude, of glutamatergic miniature excitatory postsynaptic currents (mEPSCs) recorded 2–3 days after injury, without altering miniature inhibitory postsynaptic current frequency or amplitude at this time point. Meanwhile, incision at P17 failed to affect excitatory or inhibitory synaptic function at 2–3 days postinjury. The elevated mEPSC frequency was accompanied by increased inward rectification of evoked -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)–mediated currents, but no change in AMPAR/N-methyl-d-aspartate receptor ratios, and was followed by a persistent reduction in mEPSC frequency by 9–10 days postinjury. Prolonged blockade of primary afferent input from the time of injury was achieved by administration of bupivacaine hydroxide or tetrodotoxin to the sciatic nerve at P3. The increase in mEPSC frequency evoked by P3 incision was prevented by blocking sciatic nerve activity. These results demonstrate that increased afferent input associated with peripheral tissue injury selectively modulates excitatory synaptic drive onto developing spinal sensory neurons and that the enhanced glutamatergic signaling in the dorsal horn following neonatal surgical incision is activity dependent.

Temporal Development of Anticipatory Reflex Modulation to Dynamical Interactions During Arm Movement

Kimura, T., Gomi, H. — Mon, 19 Oct 2009 09:34:41 PDT

It is known that somatosensory reflex during voluntary arm movement is modulated anticipatorily according to given tasks or environments. However, when and how reflex amplitude is set remains controversial. Is the reflex modulation completed preparatorily before movement execution or does it vary with the movement? Is the reflex amplitude coded in a temporal manner or in a spatial (or state-dependent) manner? Here we studied these issues while subjects performed planar reaching movements with upcoming opposite (rightward/leftward) directions of force fields. Somatosensory reflex responses of shoulder muscles induced by a small force perturbation were evaluated at several points before the arm encountered predictable force fields after movement start. We found that the shoulder flexor reflex responses were generally higher for the rightward than for the leftward upcoming force fields, whereas the extensor reflex responses were higher for the leftward force field. This reflex amplitude depending on the upcoming force field direction became prominent as the reflex was evoked closer to the force fields, indicating continuous changes in reflex modulation during movement. An additional experiment further showed that the reflex modulation developed as a function of the temporal distance to the force fields rather than the spatial distance. Taken together, the results suggest that, in the force field interaction task, somatosensory reflex amplitude during the course of movement is set anticipatorily on the basis of an estimate of the time-to-contact rather than the state-to-contact, to upcoming dynamical interaction during voluntary movement.

Motion Perception During Variable-Radius Swing Motion in Darkness

Rader, A. A., Oman, C. M., Merfeld, D. M. — Mon, 19 Oct 2009 09:34:41 PDT

Using a variable-radius roll swing motion paradigm, we examined the influence of interaural (y-axis) and dorsoventral (z-axis) force modulation on perceived tilt and translation by measuring perception of horizontal translation, roll tilt, and distance from center of rotation (radius) at 0.45 and 0.8 Hz using standard magnitude estimation techniques (primarily verbal reports) in darkness. Results show that motion perception was significantly influenced by both y- and z-axis forces. During constant radius trials, subjects' perceptions of tilt and translation were generally almost veridical. By selectively pairing radius (1.22 and 0.38 m) and frequency (0.45 and 0.8 Hz, respectively), the y-axis acceleration could be tailored in opposition to gravity so that the combined y-axis gravitoinertial force (GIF) variation at the subject's ears was reduced to ~0.035 m/s² – in effect, the y-axis GIF was "nulled" below putative perceptual threshold levels. With y-axis force nulling, subjects overestimated their tilt angle and underestimated their horizontal translation and radius. For some y-axis nulling trials, a radial linear acceleration at twice the tilt frequency (0.25 m/s² at 0.9 Hz, 0.13 m/s² at 1.6 Hz) was simultaneously applied to reduce the z-axis force variations caused by centripetal acceleration and by changes in the z-axis component of gravity during tilt. For other trials, the phase of this radial linear acceleration was altered to double the magnitude of the z-axis force variations. z-axis force nulling further increased the perceived tilt angle and further decreased perceived horizontal translation and radius relative to the y-axis nulling trials, while z-axis force doubling had the opposite effect. Subject reports were remarkably geometrically consistent; an observer model-based analysis suggests that perception was influenced by knowledge of swing geometry.

How Reliable is the Pattern Adaptation Technique? A Modeling Study

Hegde, J. — Mon, 19 Oct 2009 09:34:41 PDT

Upon prolonged viewing of a sinusoidal grating, the visual system is selectively desensitized to the spatial frequency of the grating, while the sensitivity to other spatial frequencies remains largely unaffected. This technique, known as pattern adaptation, has been so central to the psychophysical study of the mechanisms of spatial vision that it is sometimes referred to as the "psychologist's microelectrode." While this approach implicitly assumes that the adaptation behavior of the system is diagnostic of the corresponding underlying neural mechanisms, this assumption has never been explicitly tested. We tested this assumption using adaptation bandwidth, or the range of spatial frequencies affected by adaptation, as a representative measure of adaptation. We constructed an intentionally simple neuronal ensemble model of spatial frequency processing and examined the extent to which the adaptation bandwidth at the system level reflected the bandwidth at the neuronal level. We find that the adaptation bandwidth could vary widely even when all spatial frequency tuning parameters were held constant. Conversely, different spatial frequency tuning parameters were able to elicit similar adaptation bandwidths from the neuronal ensemble. Thus, the tuning properties of the underlying units did not reliably reflect the adaptation bandwidth at the system level, and vice versa. Furthermore, depending on the noisiness of adaptation at the neural level, the same neuronal ensemble was able to produce selective or nonselective adaptation at the system level, indicating that a lack of selective adaptation at the system level cannot be taken to mean a lack of tuned mechanisms at the neural level. Together, our results indicate that pattern adaptation cannot be used to reliably estimate the tuning properties of the underlying units, and imply, more generally, that pattern adaptation is not a reliable tool for studying the neural mechanisms of pattern analysis.

Hemispheric Lateralization of Pain Processing by Amygdala Neurons

Ji, G., Neugebauer, V. — Mon, 19 Oct 2009 09:34:41 PDT

Recent biochemical and behavioral data suggest right-hemispheric lateralization of amygdala functions in pain. Our previous electrophysiological studies showed pain-related neuroplasticity in the latero-capsular division of the central nucleus of the amygdala (CeLC) in the right brain hemisphere. Here we determined differences in the processing of pain-related signals in right versus left CeLC neurons. Individual CeLC neurons were recorded extracellularly before and after induction of an arthritis pain state in anesthetized rats. Brief innocuous and noxious test stimuli were applied to peripheral tissues ipsi- and contralateral to the recording site. A monoarthritis was induced in the ipsi- or contralateral knee by intraarticular injections of kaolin and carrageenan. Under normal conditions, CeLC neurons in the left amygdala had smaller receptive fields than those in the right, but the magnitude of background and evoked activity was not significantly different. After arthritis induction, neurons in the right, but not left, CeLC developed increased background activity and evoked responses, irrespective of the location of the arthritis (ipsi- or contralateral to the recording site). A protein kinase A (PKA) inhibitor decreased the activity of right CeLC neurons after arthritis induction but had no effect in the left amygdala. Forskolin, however, increased the activity of left and right CeLC neurons under normal conditions. The results show for the first time laterality of pain-related electrophysiological activity changes in individual amygdala neurons. Whereas both left and right amygdala neurons receive nociceptive inputs and can become sensitized in principle, a yet unknown mechanism prevents PKA activation and pain-related changes in the left amygdala.

Motor Unit Rotation in a Variety of Human Muscles

Bawa, P., Murnaghan, C. — Mon, 19 Oct 2009 09:34:41 PDT

The phenomena of substitution and rotation among motor units of a muscle were examined in seven different muscles. Intramuscular motor unit activity and surface electromyographic (EMG) activity were recorded from one of the following muscles: abductor digiti minimi, first dorsal interosseous, extensor digitorum communis, flexor and extensor carpi radialis, tibialis anterior, and soleus. The subject was asked to discharge a discernible unit at a comfortable constant or rhythmically (pseudosinusoidally) modulated rate with audio and visual feedback. Results are reported from a total of 42 sets of motor units from all seven muscles. We observed that when a subject fired a motor unit for a long period, an additional motor unit frequently started to discharge after a few minutes. When the subject was asked to keep activity down to one unit, very often it was Unit 1 that dropped and Unit 2 continued to fire. Whereas Unit 2 had fired for a few minutes, Unit 1 resumed firing without any conscious effort by the subject. If the subject was then asked to retain just one unit, it was Unit 2 that dropped. Rhythmic modulation of firing rate of a tonically firing unit showed that whereas the threshold of this unit increased, the threshold of a phasically discharging unit decreased substantially. The increase in threshold of a tonically discharging unit is suggested to arise from inactivation of Na⁺ and Ca²⁺ channels and the decrease in threshold of higher-threshold units is suggested to arise from an increase in persistent inward currents that may occur during prolonged contractions. Whether a unit stops or starts to fire is suggested to depend on a balance between the strength of the central motor command, persistent inward currents, and inactivation of voltage-gated channels. Such rotations among low-threshold motoneurons would ensure low-level sustained contractions to be viable not only in small hand muscles but also in larger limb muscles.

SK Channels Gate Information Processing In Vivo by Regulating an Intrinsic Bursting Mechanism Seen In Vitro

Toporikova, N., Chacron, M. J. — Mon, 19 Oct 2009 09:34:41 PDT

Understanding the mechanistic substrates of neural computations that lead to behavior remains a fundamental problem in neuroscience. In particular, the contributions of intrinsic neural properties such as burst firing and dendritic morphology to the processing of behaviorally relevant sensory input have received much interest recently. Pyramidal cells within the electrosensory lateral line lobe of weakly electric fish display an intrinsic bursting mechanism that relies on somato-dendritic interactions when recorded in vitro: backpropagating somatic action potentials trigger dendritic action potentials that lead to a depolarizing afterpotential (DAP) at the soma. We recorded intracellularly from these neurons in vivo and found firing patterns that were quite different from those seen in vitro: we found no evidence for DAPs as each somatic action potential was followed by a pronounced afterhyperpolarization (AHP). Calcium chelators injected in vivo reduced the AHP, thereby unmasking the DAP and inducing in vitro-like bursting in pyramidal cells. These bursting dynamics significantly reduced the cell's ability to encode the detailed time course of sensory input. We performed additional in vivo pharmacological manipulations and mathematical modeling to show that calcium influx through N-methyl-d-aspartate (NMDA) receptors activate dendritic small conductance (SK) calcium-activated potassium channels, which causes an AHP that counteracts the DAP and leads to early termination of the burst. Our results show that ion channels located in dendrites can have a profound influence on the processing of sensory input by neurons in vivo through the modulation of an intrinsic bursting mechanism.

Anatomical and Electrophysiological Comparison of CA1 Pyramidal Neurons of the Rat and Mouse

Routh, B. N., Johnston, D., Harris, K., Chitwood, R. A. — Mon, 19 Oct 2009 09:34:42 PDT

The study of learning and memory at the single-neuron level has relied on the use of many animal models, most notably rodents. Although many physiological and anatomical studies have been carried out in rats, the advent of genetically engineered mice has necessitated the comparison of new results in mice to established results from rats. Here we compare fundamental physiological and morphological properties and create three-dimensional compartmental models of identified hippocampal CA1 pyramidal neurons of one strain of rat, Sprague–Dawley, and two strains of mice, C57BL/6 and 129/SvEv. We report several differences in neuronal physiology and anatomy among the three animal groups, the most notable being that neurons of the 129/SvEv mice, but not the C57BL/6 mice, have higher input resistance, lower dendritic surface area, and smaller spines than those of rats. A surprising species-specific difference in membrane resonance indicates that both mouse strains have lower levels of the hyperpolarization-activated nonspecific cation current I_h. Simulations suggest that differences in I_h kinetics rather than maximal conductance account for the lower resonance. Our findings indicate that comparisons of data obtained across strains or species will need to account for these and potentially other physiological and anatomical differences.

Acute Changes in Motor Cortical Excitability During Slow Oscillatory and Constant Anodal Transcranial Direct Current Stimulation

Bergmann, T. O., Groppa, S., Seeger, M., Molle, M., Marshall, L., Siebner, H. R. — Mon, 19 Oct 2009 09:34:42 PDT

Transcranial oscillatory current stimulation has recently emerged as a noninvasive technique that can interact with ongoing endogenous rhythms of the human brain. Yet, there is still little knowledge on how time-varied exogenous currents acutely modulate cortical excitability. In ten healthy individuals we used on-line single-pulse transcranial magnetic stimulation (TMS) to search for systematic shifts in corticospinal excitability during anodal sleeplike 0.8-Hz slow oscillatory transcranial direct current stimulation (so-tDCS). In separate sessions, we repeatedly applied 30-s trials (two blocks at 20 min) of either anodal so-tDCS or constant tDCS (c-tDCS) to the primary motor hand area during quiet wakefulness. Simultaneously and time-locked to different phase angles of the slow oscillation, motor-evoked potentials (MEPs) as an index of corticospinal excitability were obtained in the contralateral hand muscles 10, 20, and 30 s after the onset of tDCS. MEPs were also measured off-line before, between, and after both stimulation blocks to detect any lasting excitability shifts. Both tDCS modes increased MEP amplitudes during stimulation with an attenuation of the facilitatory effect toward the end of a 30-s tDCS trial. No phase-locking of corticospinal excitability to the exogenous oscillation was observed during so-tDCS. Off-line TMS revealed that both c-tDCS and so-tDCS resulted in a lasting excitability increase. The individual magnitude of MEP facilitation during the first tDCS trials predicted the lasting MEP facilitation found after tDCS. We conclude that sleep slow oscillation-like excitability changes cannot be actively imposed on the awake cortex with so-tDCS, but phase-independent on-line as well as off-line facilitation can reliably be induced.

Inhibitory Transmission in Locus Coeruleus Neurons Expressing GABAA Receptor Epsilon Subunit Has a Number of Unique Properties

Mon, 19 Oct 2009 09:34:42 PDT

Fast inhibitory synaptic transmission in the brain relies on ionotropic GABA_A receptors (GABA_AR). Eighteen genes code for GABA_AR subunits, but little is known about the subunit. Our aim was to identify the synaptic transmission properties displayed by native receptors incorporating . Immunogold localization detected at synaptic sites on locus coeruleus (LC) neurons. In situ hybridization revealed prominent signals from , and mRNAs, some low β1 and β3 signals, and no signal. Using in vivo extracellular and in vitro patch-clamp recordings in LC, we established that neuron firing rates, GABA-activated currents, and mIPSC charge were insensitive to the benzodiazepine flunitrazepam (FLU), in agreement with the characteristics of recombinant receptors including an subunit. Surprisingly, LC provided binding sites for benzodiazepines, and GABA-induced currents were potentiated by diazepam (DZP) in the micromolar range. A number of GABA_AR ligands significantly potentiated GABA-induced currents, and zinc ions were only active at concentrations above 1 µM, further indicating that receptors were not composed of only and β subunits, but included an subunit. In contrast to recombinant receptors including an subunit, GABA_AR in LC showed no agonist-independent opening. Finally, we determined that mIPSCs, as well as ensemble currents induced by ultra-fast GABA application, exhibited surprisingly slow rise times. Our work thus defines the signature of native GABA_AR with a subunit composition including : differential sensitivity to FLU and DZP and slow rise time of currents. We further propose that _3, β_1/3, and subunits compose GABA_AR in LC.

Endogenous Calcium Buffering Capacity of Substantia Nigral Dopamine Neurons

Foehring, R. C., Zhang, X. F., Lee, J.C.F., Callaway, J. C. — Mon, 19 Oct 2009 09:34:42 PDT

Dopamine (DA)-containing cells from the substantia nigra pars compacta (SNc) play a major role in the initiation of movement. Loss of these cells results in Parkinson's disease (PD). Changes in intracellular calcium ion concentration ([Ca²⁺]_i) elicit several events in DA cells, including spike afterhyperpolarizations (AHPs) and subthreshold oscillations underlying autonomous firing. Continuous Ca²⁺ load due to Ca²⁺-dependent rhythmicity has been proposed to cause the death of DA cells in PD and normal aging. Because of the physiological and pathophysiological importance of [Ca²⁺]_i in DA cells, we characterized their intrinsic Ca²⁺-buffering capacity (K_S) in brain slices. We introduced a fluorescent Ca²⁺-sensitive exogenous buffer (200 µM fura-2) and cells were tracked from break-in until steady state by stimulating with a single action potential (AP) every 30 s and measuring the Ca²⁺ transient from the proximal dendrite. DA neurons filled exponentially with a of about 5–6 min. [Ca²⁺]_i was assumed to equilibrate between the endogenous Ca²⁺ buffer and the exogenous Ca²⁺ indicator buffer. Intrinsic buffering was estimated by extrapolating from the linear relationships between the amplitude or time constant of the Ca²⁺ transients versus [fura-2]. Extrapolated Ca²⁺-transients in the absence of fura-2 had mean peak amplitudes of 293.7 ± 65.3 nM and = 124 ± 13 ms (postnatal day 13 [P13] to P17 animals). Intrinsic buffering increased with age in DA neurons. For cells from animals P13–P17, K_S was estimated to be about 110 (n = 20). In older animals (P25–P32), the estimate was about 179 (n = 10). These relatively low values may reflect the need for rapid Ca²⁺ signaling, e.g., to allow activation of sK channels, which shape autonomous oscillations and burst firing. Low intrinsic buffering may also make DA cells vulnerable to Ca²⁺-dependent pathology.

Neural Activity in Primate Caudate Nucleus Associated With Pro- and Antisaccades

Ford, K. A., Everling, S. — Mon, 19 Oct 2009 09:34:42 PDT

The basal ganglia (BG) play a central role in movement and it has been demonstrated that the discharge rate of neurons in these structures are modulated by the behavioral context of a given task. Here we used the antisaccade task, in which a saccade toward a flashed visual stimulus must be inhibited in favor of a saccade to the opposite location, to investigate the role of the caudate nucleus, a major input structure of the BG, in flexible behavior. In this study, we recorded extracellular neuronal activity while monkeys performed pro- and antisaccade trials. We identified two populations of neurons: those that preferred contralateral saccades (CSNs) and those that preferred ipsilateral saccades (ISNs). CSNs increased their firing rates for prosaccades, but not for antisaccades, and ISNs increased their firing rates for antisaccades, but not for prosaccades. We propose a model in which CSNs project to the direct BG pathway, facilitating saccades, and ISNs project to the indirect pathway, suppressing saccades. This model suggests one possible mechanism by which these neuronal populations could be modulating activity in the superior colliculus.

Synaptic Noise and Physiological Coupling Generate High-Frequency Oscillations in a Hippocampal Computational Model

Stacey, W. C., Lazarewicz, M. T., Litt, B. — Mon, 19 Oct 2009 09:34:42 PDT

There is great interest in the role of coherent oscillations in the brain. In some cases, high-frequency oscillations (HFOs) are integral to normal brain function, whereas at other times they are implicated as markers of epileptic tissue. Mechanisms underlying HFO generation, especially in abnormal tissue, are not well understood. Using a physiological computer model of hippocampus, we investigate random synaptic activity (noise) as a potential initiator of HFOs. We explore parameters necessary to produce these oscillations and quantify the response using the tools of stochastic resonance (SR) and coherence resonance (CR). As predicted by SR, when noise was added to the network the model was able to detect a subthreshold periodic signal. Addition of basket cell interneurons produced two novel SR effects: 1) improved signal detection at low noise levels and 2) formation of coherent oscillations at high noise that were entrained to harmonics of the signal frequency. The periodic signal was then removed to study oscillations generated only by noise. The combined effects of network coupling and synaptic noise produced coherent, periodic oscillations within the network, an example of CR. Our results show that, under normal coupling conditions, synaptic noise was able to produce gamma (30–100 Hz) frequency oscillations. Synaptic noise generated HFOs in the ripple range (100–200 Hz) when the network had parameters similar to pathological findings in epilepsy: increased gap junctions or recurrent synaptic connections, loss of inhibitory interneurons such as basket cells, and increased synaptic noise. The model parameters that generated these effects are comparable with published experimental data. We propose that increased synaptic noise and physiological coupling mechanisms are sufficient to generate gamma oscillations and that pathologic changes in noise and coupling similar to those in epilepsy can produce abnormal ripples.

Coding of Repetitive Transients by Auditory Cortex on Heschl's Gyrus

Mon, 19 Oct 2009 09:34:42 PDT

The capacity of auditory cortex on Heschl's gyrus (HG) to encode repetitive transients was studied in human patients undergoing surgical evaluation for medically intractable epilepsy. Multicontact depth electrodes were chronically implanted in gray matter of HG. Bilaterally presented stimuli were click trains varying in rate from 4 to 200 Hz. Averaged evoked potentials (AEPs) and event-related band power (ERBP), computed from responses at each of 14 recording sites, identified two auditory fields. A core field, which occupies posteromedial HG, was characterized by a robust polyphasic AEP on which could be superimposed a frequency following response (FFR). The FFR was prominent at click rates below ~50 Hz, decreased rapidly as click rate was increased, but could reliably be detected at click rates as high as 200 Hz. These data are strikingly similar to those obtained by others in the monkey under essentially the same stimulus conditions, indicating that mechanisms underlying temporal processing in the auditory core may be highly conserved across primate species. ERBP, which reflects increases or decreases of both phase-locked and non–phase-locked power within given frequency bands, showed stimulus-related increases in gamma band frequencies as high as 250 Hz. The AEPs recorded in a belt field anterolateral to the core were typically of low amplitude, showing little or no evidence of short-latency waves or an FFR, even at the lowest click rates used. The non–phase-locked component of the response extracted from the ERBP showed a robust, long-latency response occurring here in response to the highest click rates in the series.

On the Origin of Event-Related Potentials Indexing Covert Attentional Selection During Visual Search

Cohen, J. Y., Heitz, R. P., Schall, J. D., Woodman, G. F. — Mon, 19 Oct 2009 09:34:42 PDT

Despite nearly a century of electrophysiological studies recording extracranially from humans and intracranially from monkeys, the neural generators of nearly all human event-related potentials (ERPs) have not been definitively localized. We recorded an attention-related ERP component, known as the N2pc, simultaneously with intracranial spikes and local field potentials (LFPs) in macaques to test the hypothesis that an attentional-control structure, the frontal eye field (FEF), contributed to the generation of the macaque homologue of the N2pc (m-N2pc). While macaques performed a difficult visual search task, the search target was selected earliest by spikes from single FEF neurons, later by FEF LFPs, and latest by the m-N2pc. This neurochronometric comparison provides an empirical bridge connecting macaque and human experiments and a step toward localizing the neural generator of this important attention-related ERP component.

Oculomotor Distraction by Signals Invisible to the Retinotectal and Magnocellular Pathways

Bompas, A., Sumner, P. — Mon, 19 Oct 2009 09:34:42 PDT

Irrelevant stimulus onsets interfere with saccade planning to other stimuli, prolonging saccadic latency (the oculomotor distractor effect) or eliciting directional errors (saccadic capture). Such stimulus-driven interference has been associated with the retinotectal pathway, the direct pathway from retina to superior colliculus. Consistent with this theory, the distractor effect has not been found for stimuli visible only to the short-wave cones in the retina (S cones), which are thought not to contribute to the retinotectal pathway. However, S-cone signals are generally slower than luminance signals and such differences in temporal dynamics have not been taken into account when investigating the saccadic distractor effect. Here, by varying the delay between target and distractor, we found that S-cone stimuli do in fact produce a distractor effect, but the optimal delay is generally different from that for luminance distractors. The temporal dynamics of the distractor effect conform to a general framework of saccadic competition that takes sensory transmission time into account. Additionally, we observe that S-cone stimuli are able to produce saccadic capture in our paradigm. We conclude that stimulus-driven oculomotor interference does not rely on the retinotectal pathway, or indeed the magnocellular pathway, which is also blind to our S-cone stimuli.

Dendritic Spine Remodeling After Spinal Cord Injury Alters Neuronal Signal Processing

Tan, A. M., Choi, J.-S., Waxman, S. G., Hains, B. C. — Mon, 19 Oct 2009 09:34:42 PDT

Central sensitization, a prolonged hyperexcitability of dorsal horn nociceptive neurons, is a major contributor to abnormal pain processing after spinal cord injury (SCI). Dendritic spines are micron-sized dendrite protrusions that can regulate the efficacy of synaptic transmission. Here we used a computational approach to study whether changes in dendritic spine shape, density, and distribution can individually, or in combination, adversely modify the input–output function of a postsynaptic neuron to create a hyperexcitable neuronal state. The results demonstrate that a conversion from thin-shaped to more mature, mushroom-shaped spine structures results in enhanced synaptic transmission and fidelity, improved frequency-following ability, and reduced inhibitory gating effectiveness. Increasing the density and redistributing spines toward the soma results in a greater probability of action potential activation. Our results demonstrate that changes in dendritic spine morphology, documented in previous studies on spinal cord injury, contribute to the generation of pain following SCI.

Response Properties of Fixation Neurons and Their Location in the Frontal Eye Field in the Monkey

Izawa, Y., Suzuki, H., Shinoda, Y. — Mon, 19 Oct 2009 09:34:42 PDT

Electrical stimulation of the frontal eye field (FEF) has recently been reported to suppress the generation of saccades, which supports the idea that the FEF plays a role in maintaining attentive fixation. This study analyzed the activity of fixation neurons that discharged during fixation in the FEF in relation to visual fixation and saccades in trained monkeys. The neural activity of fixation neurons increased at the start of fixation and was maintained during fixation. When a fixation spot of light disappeared during steady fixation, different fixation neurons exhibited different categories of response, ranging from a decrease in activity to an increase in activity, indicating that there is a continuum of fixation neurons, from neurons with foveal visual-related activity to neurons with activity that is related to the motor act of fixating. Fixation neurons usually showed a decrease in their firing rate before the onset of visually guided saccades (Vsacs) and memory-guided saccades in any direction. The reduction in activity of fixation neurons nearly coincided with, or occurred slightly before, the increase in the activity of saccade-related movement neurons in the FEF in the same monkey. Although fixation neurons were scattered in the FEF, about two thirds of fixation neurons were concentrated in a localized area in the FEF at which electrical stimulation induced strong suppression of the initiation of Vsacs bilaterally. These results suggest that fixation neurons in the FEF are part of a suppression mechanism that could control the maintenance of fixation and the initiation of saccades.

Involuntary Orienting of Attention to Nociceptive Events: Neural and Behavioral Signatures

Legrain, V., Perchet, C., Garcia-Larrea, L. — Mon, 19 Oct 2009 09:34:42 PDT

Pain can involuntarily capture attention and disrupt pain-unrelated cognitive activities. The brain mechanisms of these effects were explored by laser- and visual-evoked potentials. Consecutive nociceptive laser stimuli and visual stimuli were delivered in pairs. Subjects were instructed to ignore nociceptive stimuli while performing a task on visual targets. Because involuntary attention is particularly sensitive to novelty, in some trials (17%), unexpected laser stimuli were delivered on a different hand area (location-deviant) relative to the more frequent standard laser stimuli. Compared with frequent standard laser stimuli, deviant stimuli enhanced all nociceptive-evoked brain potentials (laser N1, N2, P2a, P2b). Deviant laser stimuli also decreased the amplitude of late latency–evoked responses (visual N2-P3) to the subsequent visual targets and delayed reaction times to them. The data confirm that nociceptive processing competes with pain-unrelated cognitive activities for attentional resources and that concomitant nociceptive events affect behavior by depressing attention allocation to ongoing cognitive processing. The laser-evoked potential magnitude reflected the engagement of attention to the novel nociceptive stimuli. We conclude that the laser-evoked potentials index the activity of a neural system involved in the detection of novel salient stimuli in order to focus attention and prioritize action to potentially damaging dangers.

Psychophysical Evidence for Spatiotopic Processing in Area MT in a Short-Term Memory for Motion Task

Ong, W. S., Hooshvar, N., Zhang, M., Bisley, J. W. — Mon, 19 Oct 2009 09:34:42 PDT

The middle temporal (MT) area has long been established as a cortical area involved in the encoding of motion information and has been thought to do so in retinotopic coordinates. It was previously shown that memory for motion has a spatial component by demonstrating that subjects do significantly worse on a match-to-sample task when the stimuli to be compared were spatially separated. The distance at which performance deteriorated (the critical spatial separation) increased at increasing eccentricities, suggesting that area MT was involved in the process. In this study, we asked whether optimal performance occurred when the stimuli were in the same retinotopic or spatiotopic coordinates. We found that the performance was best when the stimuli appeared in the same location in space rather than the same retinal location, after an eye movement. We also found that the relationship between retinal eccentricity and the critical spatial separation approximated that of area MT, as found previously. We conclude that area MT plays an important role in the memory for motion process and that this is carried out in spatiotopic coordinates. This conclusion supports the hypothesis that MT processing may have a spatiotopic component.

Modulation of Intrinsic Spiking in Spinal Cord Neurons

Czarnecki, A., Magloire, V., Streit, J. — Mon, 19 Oct 2009 09:34:42 PDT

The vertebrate spinal cord is equipped with a number of neuronal networks that underlie repetitive patterns of behavior as locomotion. Activity in such networks is mediated not only by intrinsic cellular properties but also by synaptic coupling. In this study, we focused on the modulation of the intrinsic activity by 5-hydroxytryptamine (5-HT, serotonin) and the cholinergic agonist muscarine in spinal cord cultures (embryonic age 14 rats). We investigated theses cultures (slices and dissociated cells) at the network level using multielectrode arrays (MEAs) and at the cellular level using whole cell patch clamp. All cultures showed bursting network activity and intrinsic activity when -aminobutyric acid, glycine, and glutamate transmission was blocked. Using MEAs, we observed an increase of the intrinsic activity in the ventral part of the slices with 5-HT and muscarine. In single-cell recordings we found that 43 and 35% of the cells that were silent in the absence of fast synaptic activity were transformed into intrinsically spiking cells by 5-HT and muscarine, respectively. We tested the hypothesis that these neuromodulators act via modulation of the persistent sodium currents (I_NaP) in these neurons. We found that 5-HT increased threefold the amplitude of I_NaP, specifically in the nonintrinsically spiking cells, and thus switched these cells into intrinsically spiking cells via activation of 5-HT₂ receptor and the phospholipase C pathway. In contrast, the effect of muscarine on nonintrinsically spiking neurons seems to be independent of I_NaP. We conclude from these findings that serotoninergic and cholinergic modulation can turn silent into spontaneously spiking neurons and thus initiate new sources of activity for rhythm generation in spinal networks.

Excitatory Roles of Protein Kinase C in Striatal Cholinergic Interneurons

Deng, P., Pang, Z.-P., Lei, Z., Xu, Z. C. — Mon, 19 Oct 2009 09:34:42 PDT

Protein kinase C (PKC) plays critical roles in neuronal activity and is widely expressed in striatal neurons. However, it is not clear how PKC activation regulates the excitability of striatal cholinergic interneurons. In the present study, we found that PKC activation significantly inhibited A-type potassium current (I_A), but had no effect on delayed rectifier potassium currents. Consistently, application of PKC activator caused an increase of firing in response to depolarizing currents in cholinergic interneurons, which was persistent in the presence of both excitatory and inhibitory neurotransmission blockers. These excitatory effects of PKC could be partially mimicked and occluded by blockade of I_A with potassium channel blocker 4-aminopyridine. In addition, immunostaining demonstrated that PKC, but not PKC and PKC, was expressed in cholinergic interneurons. Furthermore, activation of group I metabotropic glutamate receptors (mGluRs) led to an inhibition of I_A through a PKC-dependent pathway. These data indicate that activation of PKC, most likely PKC, increases the neuronal excitability of striatal cholinergic interneurons by down-regulating I_A. Group I mGluR-mediated I_A inhibition might be important for the glutamatergic regulation of cholinergic tone in the neostriatum.

Neural Substrates of Practice Structure That Support Future Off-Line Learning

Wymbs, N. F., Grafton, S. T. — Mon, 19 Oct 2009 09:34:42 PDT

Off-line learning is facilitated when motor skills are acquired under a random practice schedule and retention suffers when a similar set of motor skills are practiced under a blocked schedule. The current study identified the neural correlates of a random training schedule while participants learned a set of four-element finger sequences using their nondominant hand during functional magnetic resonance imaging. A go/no go task was used to separately probe brain areas supporting sequence preparation and production. By the end of training, the random practice schedule, relative to the block schedule, recruited a broad premotor–parietal network as well as sensorimotor and subcortical regions during both preparation and production trials, despite equivalent motor performance. Longitudinal analysis demonstrated that preparation-related activity under a random schedule remained stable or increased over time. The blocked schedule showed the opposite pattern. Across individual subjects, successful skill retention was correlated with greater activity at the end of training in the ipsilateral left motor cortex, for both preparation and production. This is consistent with recent evidence that attributes off-line learning to training-related processing within primary motor cortex. These results reflect the importance of an overlooked aspect of motor skill learning. Specifically, how trials are organized during training—with a random schedule—provides an effective basis for the formation of enduring motor memories, through enhanced engagement of core regions involved in the active preparation and implementation of motor programs.

Zebrafish Motor Neuron Subtypes Differ Electrically Prior to Axonal Outgrowth

Moreno, R. L., Ribera, A. B. — Mon, 19 Oct 2009 09:34:43 PDT

Different muscle targets and transcription factor expression patterns reveal the presence of motor neuron subtypes. However, it is not known whether these subtypes also differ with respect to electrical membrane properties. To address this question, we studied primary motor neurons (PMNs) in the spinal cord of zebrafish embryos. PMN genesis occurs during gastrulation and gives rise to a heterogeneous set of motor neurons that differ with respect to transcription factor expression, muscle targets, and soma location within each spinal cord segment. The unique subtype-specific soma locations and axonal trajectories of two PMNs—MiP (middle) and CaP (caudal)—allowed their identification in situ as early as 17 h postfertilization (hpf), prior to axon genesis. Between 17 and 48 hpf, CaPs and MiPs displayed subtype-specific electrical membrane properties. Voltage-dependent inward and outward currents differed significantly between MiPs and CaPs. Moreover, by 48 hpf, CaPs and MiPs displayed subtype-specific firing behaviors. Our results demonstrate that motor neurons that differ with respect to muscle targets and transcription factor expression acquire subtype-specific electrical membrane properties. Moreover, the differences are evident prior to axon genesis and persist to the latest stage studied, 2 days postfertilization.

Social Context Rapidly Modulates the Influence of Auditory Feedback on Avian Vocal Motor Control

Sakata, J. T., Brainard, M. S. — Mon, 19 Oct 2009 09:34:43 PDT

Sensory feedback is important for the learning and control of a variety of behaviors. Vocal motor production in songbirds is a powerful model system to study sensory influences on behavior because the learning, maintenance, and control of song are critically dependent on auditory feedback. Based on previous behavioral and neural experiments, it has been hypothesized that songs produced in isolation [undirected (UD) song] represent a form of vocal practice, whereas songs produced to females during courtship interactions [female-directed (FD) song] represent a form of vocal performance. According to this "practice versus performance" framework, auditory feedback should be more influential when birds engage in vocal practice than when they engage in vocal performance. To directly test this hypothesis, we used a computerized system to perturb auditory feedback at precise locations during the songs of Bengalese finches and compared the degree to which feedback perturbations caused song interruptions as well as changes to the sequencing and timing of syllables between interleaved renditions of UD and FD song. We found that feedback perturbation caused fewer song interruptions and smaller changes to syllable timing during FD song than during UD song. These data show that changes in the social context in which song is produced rapidly modulate the influence of auditory feedback on song control in a manner consistent with the practice versus performance framework. More generally, they indicate that, for song, as for other motor skills including human speech, the influence of sensory feedback on activity within vocal premotor circuitry can be dynamically modulated.

Recruitment in Retractor Bulbi Muscle During Eyeblink Conditioning: EMG Analysis and Common-Drive Model

Lepora, N. F., Porrill, J., Yeo, C. H., Evinger, C., Dean, P. — Mon, 19 Oct 2009 09:34:43 PDT

To analyze properly the role of the cerebellum in classical conditioning of the eyeblink and nictitating membrane (NM) response, the control of conditioned response dynamics must be better understood. Previous studies have suggested that the control signal is linearly related to the CR as a result of recruitment within the accessory abducens motoneuron pool, which acts to linearize retractor bulbi muscle and NM response mechanics. Here we investigate possible recruitment mechanisms. Data came from simultaneous recordings of NM position and multiunit electromyographic (EMG) activity from the retractor bulbi muscle of rabbits during eyeblink conditioning, in which tone and periocular shock act as conditional and unconditional stimuli, respectively. Action potentials (spikes) were extracted and classified by amplitude. Firing rates of spikes with different amplitudes were analyzed with respect to NM response temporal profiles and total EMG spike firing rate. Four main regularities were revealed and quantified: 1) spike amplitude increased with response amplitude; 2) smaller spikes always appeared before larger spikes; 3) subsequent firing rates covaried for spikes of different amplitude, with smaller spikes always firing at higher rates than larger ones; and 4) firing-rate profiles were approximately Gaussian for all amplitudes. These regularities suggest that recruitment does take place in the retractor bulbi muscle during conditioned NM responses and that all motoneurons receive the same command signal (common-drive hypothesis). To test this hypothesis, a model of the motoneuron pool was constructed in which motoneurons had a range of intrinsic thresholds distributed exponentially, with threshold linearly related to EMG spike amplitude. Each neuron received the same input signal as required by the common-drive assumption. This simple model reproduced the main features of the data, suggesting that conditioned NM responses are controlled by a common-drive mechanism that enables simple commands to determine response topography in a linear fashion.

Balance of Inhibitory and Excitatory Synaptic Activity Is Altered in Fast-Spiking Interneurons in Experimental Cortical Dysplasia

Zhou, F.-W., Chen, H.-X., Roper, S. N. — Mon, 19 Oct 2009 09:34:43 PDT

Cortical dysplasia (CD) is a common cause of intractable epilepsy in children and adults. We have studied rats irradiated in utero as a model of CD to better understand mechanisms that underlie dysplasia-associated epilepsy. Prior studies have shown a reduction in the number of cortical interneurons and in the frequency of inhibitory postsynaptic currents (IPSCs) in pyramidal cells in this model. They have also shown a reduced frequency of spontaneous and miniature excitatory postsynaptic currents (EPSCs) in the surviving cortical interneurons. However, the inhibitory synaptic contacts were not examined in that study. The current experiments were performed to assess inhibitory synaptic activity in fast-spiking (FS) interneurons in irradiated rats and controls and the balance of excitatory and inhibitory synaptic activity in these cells. Whole cell recordings were obtained from layer IV FS cells in controls and comparable FS cells in irradiated rats. The frequency of spontaneous and miniature IPSCs was reduced in dysplastic cortex, but the amplitude of these currents was unchanged. Stimulus-evoked IPSCs showed short-term depression in control and short-term facilitation in dysplastic cortex. Simultaneous recording of spontaneous EPSCs and IPSCs showed a shift in the ratio of excitation-to-inhibition in favor of inhibition in FS cells from dysplastic cortex. The same shift toward inhibition was seen when miniature EPSCs and IPSCs were examined. These results show that FS cells in dysplastic cortex have a relative lack of excitatory drive. This may result in an important class of inhibitory cells that are less able to perform their normal function especially in periods of increased excitatory activity.

Beyond the Reward Pathway: Coding Reward Magnitude and Error in the Rat Subthalamic Nucleus

Lardeux, S., Pernaud, R., Paleressompoulle, D., Baunez, C. — Mon, 19 Oct 2009 09:34:43 PDT

It was recently shown that subthalamic nucleus (STN) lesions affect motivation for food, cocaine, and alcohol, differentially, according to either the nature of the reward or the preference for it. The STN may thus code a reward according to its value. Here, we investigated how the firing of subthalamic neurons is modulated during expectation of a predicted reward between two possibilities (4 or 32% sucrose solution). The firing pattern of neurons responding to predictive cues and to reward delivery indicates that STN neurons can be divided into subpopulations responding specifically to one reward and less or giving no response to the other. In addition, some neurons ("oops" neurons) specifically encode errors as they respond only during error trials. These results reveal that the STN plays a critical role in ascertaining the value of the reward and seems to encode that value differently depending on the magnitude of the reward. These data highlight the importance of the STN in the reward circuitry of the brain.

Synchronization of GABAergic Inputs to CA3 Pyramidal Cells Precedes Seizure-Like Event Onset in Juvenile Rat Hippocampal Slices

Lasztoczi, B., Nyitrai, G., Heja, L., Kardos, J. — Mon, 19 Oct 2009 09:34:43 PDT

Here we address how dynamics of glutamatergic and GABAergic synaptic input to CA3 pyramidal cells contribute to spontaneous emergence and evolution of recurrent seizure-like events (SLEs) in juvenile (P10-13) rat hippocampal slices bathed in low-[Mg²⁺] artificial cerebrospinal fluid. In field potential recordings from the CA3 pyramidal layer, a short epoch of high-frequency oscillation (HFO; 400–800 Hz) was observed during the first 10 ms of SLE onset. GABAergic synaptic input currents to CA3 pyramidal cells were synchronized and coincided with HFO, whereas the glutamatergic input lagged by ~10 ms. If the intracellular [Cl^–] remained unperturbed (cell-attached recordings) or was set high with whole cell electrode solution, CA3 pyramidal cell firing peaked with HFO and GABAergic input. By contrast, with low intracellular [Cl^–], spikes of CA3 pyramidal cells lagged behind HFO and GABAergic input. This temporal arrangement of HFO, synaptic input sequence, synchrony of GABAergic currents, and pyramidal cell firing emerged gradually with preictal discharges until the SLE onset. Blockade of GABA_A receptor-mediated currents by picrotoxin reduced the inter-SLE interval and the number of preictal discharges and did not block recurrent SLEs. Our data suggest that dynamic changes of the functional properties of GABAergic input contribute to ictogenesis and GABAergic and glutamatergic inputs are both excitatory at the instant of SLE onset. At the SLE onset GABAergic input contributes to synchronization and recruitment of pyramidal cells. We conjecture that this network state is reached by an activity-dependent shift in GABA reversal potential during the preictal phase.

Transgenic Silencing of Neurons in the Mammalian Brain by Expression of the Allatostatin Receptor (AlstR)

Mon, 19 Oct 2009 09:34:43 PDT

The mammalian brain is an enormously complex set of circuits composed of interconnected neuronal cell types. The analysis of central neural circuits will be greatly served by the ability to turn off specific neuronal cell types while recording from others in intact brains. Because drug delivery cannot be restricted to specific cell types, this can only be achieved by putting "silencer" transgenes under the control of neuron-specific promoters. Towards this end we have created a line of transgenic mice putting the Drosophila allatostatin (AL) neuropeptide receptor (AlstR) under the control of the tetO element, thus enabling its inducible expression when crossed to tet-transactivator lines. Mammals have no endogenous AL or AlstR, but activation of exogenously expressed AlstR in mammalian neurons leads to membrane hyperpolarization via endogenous G-protein-coupled inward rectifier K⁺ channels, making the neurons much less likely to fire action potentials. Here we show that this tetO/AlstR line is capable of broadly expressing AlstR mRNA in principal neurons throughout the forebrain when crossed to a commercially-available transactivator line. We electrophysiologically characterize this cross in hippocampal slices, demonstrating that bath application of AL leads to hyperpolarization of CA1 pyramidal neurons, making them refractory to the induction of action potentials by injected current. Finally, we demonstrate the ability of AL application to silence the sound-evoked spiking responses of auditory cortical neurons in intact brains of AlstR/tetO transgenic mice. When crossed to other transactivator lines expressing in defined neuronal cell types, this AlstR/tetO line should prove a very useful tool for the analysis of intact central neural circuits.

Recovery of Slow Potentials in AC-Coupled Electrocorticography: Application to Spreading Depolarizations in Rat and Human Cerebral Cortex

Mon, 19 Oct 2009 09:34:43 PDT

Cortical spreading depolarizations (spreading depressions and peri-infarct depolarizations) are a pathology intrinsic to acute brain injury, generating large negative extracellular slow potential changes (SPCs) that, lasting on the order of minutes, are studied with DC-coupled recordings in animals. The spreading SPCs of depolarization waves are observed in human cortex with AC-coupled electrocorticography (ECoG), although SPC morphology is distorted by the high-pass filter stage of the amplifiers. Here, we present a signal processing method to reverse these distortions and recover approximate full-band waveforms from AC-coupled recordings. We constructed digital filters that reproduced the phase and amplitude distortions introduced by specific AC-coupled amplifiers and, based on this characterization, derived digital inverse filters to remove these distortions from ECoG recordings. Performance of the inverse filter was validated by its ability to recover both simulated and real low-frequency input test signals. The inverse filter was then applied to AC-coupled ECoG recordings from five patients who underwent invasive monitoring after aneurysmal subarachnoid hemorrhage. For 117 SPCs, the inverse filter recovered full-band waveforms with morphologic characteristics typical of the negative DC shifts recorded in animals. Compared with those recorded in the rat cortex with the same analog and digital methods, the negative DC shifts of human depolarizations had significantly greater durations (1:47 vs. 0:45 min:sec) and peak-to-peak amplitudes (10.1 vs. 4.2 mV). The inverse filter thus permits the study of spreading depolarizations in humans, using the same assessment of full-band DC potentials as that in animals, and suggests a particular solution for recovery of biosignals recorded with frequency-limited amplifiers.