In this Issue
REVIEW | Decision Making: Neural Mechanisms
RESEARCH ARTICLES | Auditory System Plasticity
- Muscarinic acetylcholine receptors control baseline activity and Hebbian stimulus timing-dependent plasticity in fusiform cells of the dorsal cochlear nucleus
This study is the first to use a novel method of atropine infusion directly into the fusiform cell layer of the DCN coupled with simultaneous recordings of neural activity to clarify the contribution of muscarinic acetylcholine receptors (mAChRs) to in vivo fusiform cell baseline activity and auditory-somatosensory plasticity. We have determined that blocking the mAChRs increases the synchronization of spiking activity across the fusiform cell population and induces a dominant pattern of inversion in their stimulus timing-dependent plasticity. These modifications are consistent with similar changes established in previous tinnitus studies, suggesting that mAChRs might have a critical contribution in mediating the maladaptive alterations associated with tinnitus pathology. Blocking mAChRs also resulted in decreased fusiform cell spontaneous firing rates, which is in contrast with their tinnitus hyperactivity, suggesting that changes in the interactions between the cholinergic and GABAergic systems might also be an underlying factor in tinnitus pathology.
- Principles of auditory processing differ between sensory and premotor structures of the songbird forebrain
Neural responses to auditory stimulation in sensory area NCM and premotor area HVC of the songbird forebrain show plasticity in the form of stimulus-specific adaptation with markedly different dynamics. These two structures also differ in stimulus representations and internal functional correlations. Accordingly, NCM seems to process the individually specific complex vocalizations of others based on prior familiarity, while HVC responses appear to be modulated by transitions and/or timing in the ongoing sequence of sounds.
- Broadened population-level frequency tuning in the auditory cortex of tinnitus patients
Although subjective tinnitus is one of the most common public health concerns that impair the quality of life of many individuals, no standard treatment or objective diagnostic method currently exists. We herein revealed that population-level frequency tuning was significantly broader in the tinnitus ear than in the nontinnitus ear. The results of the present study provide an insight into the development of an objective diagnostic method for subjective tinnitus.
- Stability and plasticity in neural encoding of linguistically relevant pitch patterns
We examine the timescale of experience-dependent auditory plasticity to linguistically relevant pitch patterns. We find extreme stability in lifelong experience-dependent plasticity. We further demonstrate that subcortical function in adolescents and adults is modulated by a single session of sound-to-category training. Our results suggest that behavioral relevance is a necessary ingredient for neural changes in pitch encoding to be observed throughout human development. These findings contribute to the neurophysiological understanding of long- and short-term experience-dependent modulation of pitch.
RESEARCH ARTICLES | Cellular and Molecular Properties of Neurons
- Dicer maintains the identity and function of proprioceptive sensory neurons
We have demonstrated that selectively impairing Dicer in parvalbumin-positive neurons, which include the proprioceptors, triggers behavioral changes, a lack of muscle connectivity, and a loss of transcriptional identity as observed through RNA sequencing. These results suggest that Dicer and, most likely by extension, microRNAs are crucially important for maintaining proprioception. Additionally, this study hints at the larger question of how neurons maintain their functional and molecular specificity.
- Nitric oxide promotes GABA release by activating a voltage-independent Ca2+ influx pathway in retinal amacrine cells
Our research provides evidence that nitric oxide (NO) promotes GABAergic output from retinal amacrine cells by activating a likely transient receptor potential canonical-mediated Ca2+ influx pathway. This NO-dependent mechanism promoting GABA release can be voltage independent, suggesting that, in the retina, local NO production can bypass the formal retinal circuitry and increase local inhibition.
RESEARCH ARTICLE | Central Pattern Generators
- Characteristics of breathing rate control mediated by a subregion within the pontine parabrachial complex
A circumscribed subregion of the pontine medial parabrachial nucleus plays a key role in the control of breathing frequency primarily via changes in expiratory duration. Excitation of this subregion triggers the onset of the inspiratory phase, resulting in a stereotypical ramplike phrenic activity pattern independent of time within the expiratory phase. The ability to pace the I-burst rate suggests that the in vivo I-pattern generating network must contain functioning pacemaker neurons.
RESEARCH ARTICLES | Control of Movement
- Restricted transfer of learning between unimanual and bimanual finger sequences
Studies in reaching movement demonstrated that approximately half of motor learning can transfer across unimanual and bimanual contexts, suggesting that neural representations for unimanual and bimanual movements are fairly overlapping at the level of elementary movement. In this study, we show that little or no transfer occurred across unimanual and bimanual sequential finger movements. This result suggests that bimanual sequences are represented at a level of the motor hierarchy that integrates movements of both hands.
- Rapid and flexible whole body postural responses are evoked from perturbations to the upper limb during goal-directed reaching
The present work establishes that, when reaching to a target while standing, perturbations applied to the upper limb elicit a rapid response in lower limb muscles. Unlike voluntary movements, postural responses do not occur before corrections of the upper limb. We show the first evidence that corrective postural adjustments are modulated by upper limb behavioral context (target shape). Importantly, this indicates that postural responses take into account upper limb feedback for online control.
- Segmental specificity in belly dance mimics primal trunk locomotor patterns
Belly dance provides a novel approach for studying spinal cord neural circuits. New evidence suggests that primitive locomotor circuits may be conserved in humans. Erector spinae activation patterns during the hip shimmy at different tempos are similar to those observed in salamander walking and swimming. As movement frequency increases, a sequential pattern similar to lamprey swimming emerges, suggesting that primal involuntary control mechanisms dominate in fast lateral rhythmic spine undulations even in humans.
- Spinal cord direct current stimulation differentially modulates neuronal activity in the dorsal and ventral spinal cord
Spinal cord direct current stimulation (sDCS) modulates spinal functions and shows potential for neural rehabilitation after motor systems injury. Using a multichannel electrode array, we found that cathodal DCS enhanced, and anodal depressed, M1-evoked local field potentials, network oscillations, neuronal activity, and neuronal synchrony, especially in the ventral horn. With this new understanding, it is hoped that sDCS can be developed into a tunable spinal neuromodulatory tool for promoting function after brain or spinal injury.
- Proximal-distal differences in movement smoothness reflect differences in biomechanics
This article presents the first thorough characterization of the smoothness of wrist rotations (flexion-extension and radial-ulnar deviation) and comparison with the smoothness of reaching (shoulder-elbow) movements. We found wrist rotations to be significantly less smooth than reaching movements and determined that this difference reflects proximal-distal differences in biomechanics: the greater impedance (inertia, damping, stiffness) of the shoulder-elbow filters noise in the command signal more than the impedance of the wrist.
RESEARCH ARTICLES | Higher Neural Functions and Behavior
- Differential effect of visual motion adaption upon visual cortical excitability
We examined the influence of visual motion adaptation on visual cortex excitability and found a differential effect in V1/V2 compared with V5/MT. Changes in visual excitability following motion adaptation were not related to the degree of an individual's visual dependency.
- Operant conditioning of neural activity in freely behaving monkeys with intracranial reinforcement
Closed-loop brain-computer interfaces (BCI) were used to operantly condition increases in muscle and neural activity in monkeys by delivering activity-dependent stimuli to an intracranial reinforcement site (nucleus accumbens). We conditioned increased firing rates with the monkeys seated in a training booth and also, for the first time, during free behavior in a cage using an autonomous head-fixed BCI.
RESEARCH ARTICLE | Nervous System Pathophysiology
- Dopaminergic treatment weakens medium spiny neuron collateral inhibition in the parkinsonian striatum
With the use of a large database, this study establishes that neighboring homotypic striatal spiny projection neurons have a 50% chance to form one-way collateral inhibitory connection, a substantially higher rate than previous estimates. This study also shows that dopamine denervation may alter presynaptic dopamine receptor function such that dopaminergic treatment of Parkinson's disease can weaken the surround inhibition and may reduce the contrast of the striatal outputs, potentially contributing to dopamine's profound motor and nonmotor behavioral effects.
RESEARCH ARTICLES | Neural Circuits
- Forward and inverse effects of the complete electrode model in neonatal EEG
The effect of the complete electrode model on electroencephalography forward and inverse computations is explored. A realistic neonatal head model, including a skull structure with fontanels and sutures, is used. The electrode and skull modeling differences are analyzed and compared with each other. The results suggest that the complete electrode model can be considered as an integral part of the outer head model. To achieve optimal source localization results, accurate electrode modeling might be necessary.
- Modeling fast and slow gamma oscillations with interneurons of different subtype
The oscillatory coordination of neural signals is crucial to healthy brain function. We have developed an idealized neuronal model that generates distinct fast and slow gamma oscillations, a known feature of the rodent hippocampus. Our work provides a mechanism of this phenomenon, as well as a theoretical framework for future experiments concerning hippocampal gamma. It moreover offers a tractable model of competitive gamma oscillations that is generalizable across the nervous system.
- Coupling multielectrode array recordings with silver labeling of recording sites to study cervical spinal network connectivity
We describe a method that reliably identifies the locations of multielectrode array (MEA) recording sites while preserving the surrounding tissue for immunohistochemistry. To our knowledge, this is the first cost-effective method to identify the anatomic locations of neuronal ensembles recorded with a MEA during acute preparations without the requirement of specialized array electrodes. In addition, evaluation of activity recorded from silver-labeled sites revealed a previously unappreciated degree of connectivity between midcervical interneurons.
- Intrinsic functional architecture of the macaque dorsal and ventral lateral frontal cortex
Resting-state functional MRI is used as a complementary method to invasive techniques to inform current debates on the organization of the macaque lateral frontal cortex. Given that the macaque cortex serves as a model for the human cortex, our results help generate more fine-tuned hypothesis for the organization of the human lateral frontal cortex.
- Dorsal vs. ventral differences in fast Up-state-associated oscillations in the medial prefrontal cortex of the urethane-anesthetized rat
We demonstrate, in the urethane-anesthetized rat, that within the medial prefrontal cortex (mPFC) there are clear subregional differences in the fast network oscillations associated with the slow oscillation Up-state. These differences, particularly between the dorsal and ventral subregions of the mPFC, may reflect the different functions and connectivity of these subregions.
- Physiological processes influencing motor-evoked potential duration with voluntary contraction
Muscle contraction is associated with a significant increase in motor-evoked potential (MEP) duration and amplitude. Whereas the increase in MEP duration was linear, the amplitude increase exhibited a ceiling effect. Importantly, the MEP duration increase strongly correlated with short interval-intracortical inhibition, a biomarker of motor cortical function. This suggests that whereas similar physiological processes contribute to changes in facilitated MEP duration and amplitude, cortical mechanisms appear to contribute to MEP duration changes.
- Electrical stimulation of superior colliculus affects strabismus angle in monkey models for strabismus
Electrical stimulation of the superior colliculus in strabismic monkeys results in a change in eye misalignment. These data support the notion of developmental disruption of vergence circuits leading to maintenance of eye misalignment.
- Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip
Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the connection and communication of several brain regions, underlining the importance of developing multiregional brain in vitro models. We introduced a novel brain-on-a-chip model, implementing essential in vivo features, such as different brain areas and their functional connections.
RESEARCH ARTICLES | Sensory Processing
- Functional characterization and spatial clustering of visual cortical neurons in the predatory grasshopper mouse Onychomys arenicola
Carnivores and primates possess a map for orientation selectivity in primary visual cortex (V1), whereas rodents and lagomorphs lack this organization. We examine, for the first time, V1 of a wild carnivorous rodent with predatory behaviors, the grasshopper mouse (Onychomys arenicola). We demonstrate the cellular organization of V1 in the grasshopper mouse is largely the same as the C57/BL6 laboratory mouse, suggesting that V1 neuron properties across rodent species are largely conserved.
- Spectral and spatial tuning of onset and offset response functions in auditory cortical fields A1 and CL of rhesus macaques
In the current study, we examine the relationship between the tuning of neural responses evoked by the onset and offset of acoustic stimuli in the primary auditory cortex, as well as a higher-order auditory area—the caudolateral belt field—in awake rhesus macaques. In these areas, the relationship between onset and offset response profiles in frequency and space domains formed a continuum, ranging from highly overlapping to highly nonoverlapping.
- The inion response revisited: evidence for a possible cerebellar contribution to vestibular-evoked potentials produced by air-conducted sound stimulation
Loud sounds were used to activate vestibular receptors in human volunteers and the effects of head and eye position studied for short-latency responses. A potential (p10/n17) recorded in the parieto-occipital leads showed behavior not expected for a response with a myogenic origin. Source modeling suggested a possible origin from the cerebellum. It may represent a new indicator of human vestibulocerebellar function.
- Presynaptic gain control by endogenous cotransmission of dopamine and GABA in the olfactory bulb
Sensory systems, including the olfactory system, encode information across a large dynamic range, making synaptic mechanisms of gain control critical to proper function. Here we demonstrate that a dual-transmitter interneuron in the olfactory bulb controls the gain of intraglomerular afferent input via two distinct mechanisms, presynaptic inhibition as well as inhibition of a principal neuron subtype, and thereby potently controls the synaptic gain of afferent inputs.
- Descending antinociception induced by secondary somatosensory cortex stimulation in experimental neuropathy: role of the medullospinal serotonergic pathway
Stimulation of S2 cortex, but not that of an adjacent cortical area, induced descending heat antinociception in rats with the spinal nerve ligation-induced model of neuropathy. Antinociception was bilateral, and it involved suppression of pronociceptive medullary cells and activation of serotonergic pathways that act on the spinal 5-HT1A receptor. S2 stimulation failed to induce descending antinociceptive effect in sham-operated controls or in nerve-ligated animals that had not developed mechanical hypersensitivity.
- High-velocity stimulation evokes “dense” population response in layer 2/3 vibrissal cortex
In superficial layers of sensory cortex, only a small fraction of neurons fire most of the spontaneous and sensory evoked spikes. However, the functional relevance of such “sparse” activity remains unknown. We found that a “dense” population response is evoked by high-velocity micromotions applied to whiskers. Our results suggest that flashes of precisely timed population response on an almost silent background can provide a high capacity for coding of ecologically salient stimuli.
- Cutaneous neurturin overexpression alters mechanical, thermal, and cold responsiveness in physiologically identified primary afferents
GDNF family neurotrophic factors regulate the development and function of primary sensory neurons. Of these, neurturin has been shown to modulate mechanical and cooling sensitivity behaviorally. Here we show that overexpression of neurturin in basal keratinocytes regulates mechanical responsiveness in A-fiber primary sensory neurons while increasing the overall numbers of cold-sensing units. Results demonstrate a crucial role for cutaneous neurturin in modulating responsiveness to peripheral stimuli at the level of the primary afferent.
- Single-neuron responses to intraoral delivery of odor solutions in primary olfactory and gustatory cortex
Food perception is inherently multisensory, taking into account taste, smell, and texture qualities. However, the neural mechanisms underlying flavor perception remain unknown. Recording neural activity directly from the rat brain while animals consume multisensory flavor stimuli, we demonstrate that information about odor, taste, and mouthfeel of food converges on primary taste and smell cortex. The results suggest that processing of naturalistic, multisensory information involves an interacting network of primary sensory areas.
- Heterogeneous effects of norepinephrine on spontaneous and stimulus-driven activity in the male accessory olfactory bulb
Norepinephrine (NE) is released throughout the brain in many behavioral contexts, but its impacts on information processing are not well understood. We studied the impact of NE on chemosensory tuning in the mouse accessory olfactory bulb (AOB). Electrophysiological recordings from AOB neurons in ex vivo preparations revealed that NE, on balance, inhibited mitral cell responses to chemosensory cues. However, NE’s effects were heterogeneous, indicating that NE signaling reshapes AOB output in a cell- and stimulus-specific manner.
- Auditory adaptation improves tactile frequency perception
Auditory signals can influence the tactile perception of temporal frequency. Multiple neural mechanisms could account for the perceptual interactions between contemporaneous auditory and tactile signals. Using a crossmodal adaptation paradigm, we found that auditory adaptation causes frequency- and feature-specific improvements in tactile perception. This crossmodal transfer of aftereffects between audition and touch implies that tactile frequency perception relies on neural circuits that also process auditory frequency.
- Preparatory α-band oscillations reflect spatial gating independently of predictions regarding target identity
The present work clarifies if and how human brain oscillations in the α-band support multiple types of anticipatory attention. Using magnetoencephalography, we show that posterior α-band oscillations are modulated by predictions regarding the spatial location of an upcoming visual target, but not by feature-based predictions regarding its identity, despite robust behavioral benefits. This provides novel insights into the functional role of preparatory α mechanisms and suggests a limited specificity with which they may operate.
- Orientation selectivity in the visual cortex of the nine-banded armadillo
The current study shows that armadillo primary visual cortex (V1) neurons share the signature properties of V1 neurons of primates, carnivorans, and rodents. Furthermore, these neurons exhibit a degree of selectivity for stimulus orientation and motion direction similar to that found in primate V1. Our findings in armadillo visual cortex suggest that the functional properties of V1 neurons emerged early in the mammalian lineage, near the time of the divergence of marsupials.
RESEARCH ARTICLES | Spinal Control of Motor Outputs
- Desynchronization does not contribute to intracortical inhibition and facilitation: a paired-pulse paradigm study combined with TST
Combining the triple stimulation technique with the paired-pulse stimulation paradigm improves the consistency of short intracortical inhibition and facilitation and could be useful in research, but the interindividual variability precludes their utility for clinical practice. Our findings do not suggest that desynchronization of descending discharges following transcranial magnetic stimulation contributes to short intracortical inhibition or intracortical facilitation.
- Synaptic control of the shape of the motoneuron pool input-output function
Motoneuron activity is generally considered to reflect the level of excitatory drive. However, the activation of voltage-dependent intrinsic conductances can distort the relation between excitatory drive and the total output of a pool of motoneurons. Using a pool of realistic motoneuron models, we show that pool output can be a highly nonlinear function of synaptic input but linearity can be achieved through adjusting the time course of excitatory and inhibitory synaptic inputs.
INNOVATIVE METHODOLOGY | Neural Circuits
- Temporally precise control of single-neuron spiking by juxtacellular nanostimulation
Assessing the impact of temporal features of neuronal spike trains requires imposing arbitrary patterns of spiking on individual neurons during behavior, but this has been difficult to achieve due to limitations of existing stimulation methods. We present a technique that overcomes these limitations by using carefully designed short-duration fluctuating juxtacellular current injections, which allow for the precise and reliable evocation of arbitrary patterns of neuronal spikes in single neurons in vivo.
- Techniques to identify and temporally correlate calcium transients between multiple regions of interest in vertebrate neural circuits
Dynamic imaging of intracellular calcium is commonly used to record changes in excitability in central and peripheral neurons. We describe a novel analytical methodology that objectively discriminates calcium transients from low signal-to-noise recordings from multiple sites and quantifies the degree of temporal synchrony between events. These new methods can be applied not only to calcium imaging but also to many other physiological recordings where discrimination and temporal correlation of biological signals from multiple sites is required.
- Revealing unobserved factors underlying cortical activity with a rectified latent variable model applied to neural population recordings
The rapid development of neural recording technologies presents new opportunities for understanding patterns of activity across neural populations. Here we show how a latent variable model with appropriate nonlinear form can be used to identify sources of input to a neural population and infer their time courses. Furthermore, we demonstrate how these sources are related to behavioral contexts outside of direct experimental control.
- Modeling microelectrode biosensors: free-flow calibration can substantially underestimate tissue concentrations
Microelectrode biosensors are typically calibrated in a free-flow environment where the concentrations at the biosensor surface are constant. However, when in tissue, the analyte reaches the biosensor via diffusion and so analyte breakdown by the biosensor results in a concentration gradient and consequently a lower concentration around the biosensor. This effect means that naive free-flow calibration will underestimate tissue concentration. We develop mathematical models to better quantify the discrepancy between the calibration and tissue environment and experimentally verify our key predictions.