In this Issue
NEURO FORUM | Comparative Approaches in Neurobiology
RESEARCH ARTICLES | Auditory System Plasticity
- Neural tracking of attended versus ignored speech is differentially affected by hearing loss
The present study investigates the effect of hearing loss in older listeners on the neural tracking of competing speech. Interestingly, we observed that whereas internal degradation (hearing loss) relates to the neural tracking of ignored speech, external sound degradation (ratio between attended and ignored speech; signal-to-noise ratio) relates to tracking of attended speech. This provides the first evidence for hearing loss affecting the ability to neurally track speech.
- Passive stimulation and behavioral training differentially transform temporal processing in the inferior colliculus and primary auditory cortex
Behaviorally relevant vs. passive electric stimulation of the auditory nerve differentially affects neuronal temporal processing in the central nucleus of the inferior colliculus (ICC) and the primary auditory cortex (AI) in profoundly short-deaf and long-deaf cats. Temporal plasticity in the ICC depends on a critical amount of electric stimulation, independent of its behavioral relevance. In contrast, the AI emerges as a pivotal site for behaviorally driven neuronal temporal plasticity in the deaf auditory system.
RESEARCH ARTICLES | Cellular and Molecular Properties of Neurons
- GSG1L regulates the strength of AMPA receptor-mediated synaptic transmission but not AMPA receptor kinetics in hippocampal dentate granule neurons
GSG1L is a newly identified AMPA receptor (AMPAR) auxiliary subunit and plays a unique role in the regulation of AMPAR trafficking and function in hippocampal CA1 pyramidal neurons. However, its role in the regulation of AMPARs in hippocampal dentate granule cells remains to be characterized. The current work reveals that GSG1L regulates strength of AMPAR-mediated synaptic transmission but not the receptor kinetic properties in hippocampal dentate granule neurons.
- Clarithromycin increases neuronal excitability in CA3 pyramidal neurons through a reduction in GABAergic signaling
Clinical administration of the macrolide antibiotic clarithromycin has been associated with side effects such as mania, agitation, and delirium. Here, we investigated the adverse effects of this antibiotic on CA3 pyramidal cell excitability. Clarithromycin induces hyperexcitability in single neurons and is related to a reduction in GABAergic signaling. Our results support a potentially new application of clarithromycin as a stimulant to facilitate emergence from anesthesia or to normalize vigilance.
- Optimizing computer models of corticospinal neurons to replicate in vitro dynamics
We developed models of motor cortex corticospinal neurons that replicate in vitro dynamics, including hyperpolarization-induced sag and realistic firing patterns. Models demonstrated resonance in response to synaptic stimulation, with resonance frequency increasing in apical dendrites with increasing distance from soma, matching the increasing oscillation frequencies spanning deep to superficial cortical layers. This gradient may enable specific corticospinal neuron dendrites to entrain to relevant oscillations in different cortical layers, contributing to appropriate motor output commands.
RESEARCH ARTICLE | Central Pattern Generators
- Rhythm generation, coordination, and initiation in the vocal pathways of male African clawed frogs
Central pattern generators (CPGs) are considered to underlie vocalizations in many vertebrate species, but the detailed mechanisms underlying their functions remain unclear. We addressed this question using an isolated brain preparation of African clawed frogs. We discovered that two vocal phases are mediated by anatomically distinct CPGs, that there are a pair of CPGs contained in the left and right half of the brain stem, and that mechanisms underlying initiation of the two vocal phases are distinct.
RESEARCH ARTICLE | Control of Homeostasis
- The role of adenosine in the maturation of sleep homeostasis in rats
Brain mechanisms that regulate the maturation of sleep are understudied. The present study generated first evidence about a potential mechanistic role for adenosine in the maturation of sleep homeostasis. Specifically, we demonstrate that early postweaning development in rats, when homeostatic response to sleep loss become adult like, is characterized by maturational changes in wake-related production/release of adenosine in the brain. Pharmacologically increased adenosine signaling in developing brain facilitates homeostatic responses to sleep deprivation.
RESEARCH ARTICLES | Control of Movement
- Sensorimotor integration of vision and proprioception for obstacle crossing in ambulatory individuals with spinal cord injury
This work is unique since it examines the contribution of combined, bilateral hip and knee proprioceptive sense on the recovery of skilled walking function, in addition to characterizing gaze behavior during a skilled walking task in people with motor-incomplete spinal cord injury.
- Changes in activity of fast-spiking interneurons of the monkey striatum during reaching at a visual target
We explored the functional contributions of striatal fast-spiking interneurons (FSIs), presumed GABAergic interneurons, to distinct steps of movement generation in monkeys performing a reaching task. The activity of individual FSIs was modulated before and during the movement, consisting mostly of increased in firing rates. Changes in activity also occurred during movement preparation. We interpret this variety of modulation types at different moments of task performance as reflecting differential FSI control over distinct phases of movement.
- Beat-to-beat control of human optokinetic nystagmus slow phase durations
This study provides the first clear evidence that the generation of optokinetic nystagmus (OKN) fast phases is a decision process that is influenced by performance of a concurrent disjunctive reaction time task (DRT). The slow phase (SP) durations are consistent with a Gaussian basic interval generator and multiple interval SP durations occur more frequently in the presence of the DRT. Hence, OKN shows dual-task interference in a manner observed in voluntary movements, such as saccades.
- Does the sensorimotor system minimize prediction error or select the most likely prediction during object lifting?
Using a novel experimental model of object lifting, we tested whether the sensorimotor system models the weight of objects by minimizing lifting errors or by selecting the statistically most likely weight. We found that the sensorimotor system minimizes the square of prediction errors for object lifting. This parallels the results of studies that investigated visually guided reaching, suggesting an overlap in the underlying mechanisms between tasks that involve different sensory systems.
- On identifying kinematic and muscle synergies: a comparison of matrix factorization methods using experimental data from the healthy population
Literature on comparing factorization methods in identifying motor synergies using numerically generated, simulation, and muscle activation data from animal studies already exists. We present an empirical evaluation of the performance of three of these methods on muscle activation and joint angles data from human reaching motion: principal component analysis, nonnegative matrix factorization, and independent component analysis. Using numerical simulation, we also studied the meaning and differences in the synergy structures returned by each method. The results can be used to unify approaches in identifying and interpreting motor synergies.
- Referent control and motor equivalence of reaching from standing
Motor actions may result from minimization of the deflection of the actual body configuration from the centrally specified referent body configuration, in the limits of neuromuscular and environmental constraints. The minimization process may maintain reaching trajectory and accuracy regardless of the number of body segments involved (motor equivalence), as confirmed in this study of reaching from standing in young healthy individuals. Results suggest that the referent control process may underlie motor equivalence in reaching.
- Consolidation of visuomotor adaptation memory with consistent and noisy environments
The adaptation of movement is essential for many daily activities. To interact with targets, this often requires learning the mapping to produce appropriate motor commands based on visual input. Here, we show that a novel visuomotor mapping is retained 1 wk after initial learning in a visually guided walking task. Furthermore, we find that this motor memory consolidates (i.e., becomes more resistant to interference from learning a competing mapping) when learning in constant and noisy mapping environments.
- Evidence of common and separate eye and hand accumulators underlying flexible eye-hand coordination
Previous studies on eye-hand coordination have considered mainly the means of eye and hand reaction time (RT) distributions. Here, we leverage the approximately linear relationship between the mean and standard deviation of RT distributions, as predicted by the drift-diffusion model, to propose the existence of two distinct computational architectures underlying coordinated eye-hand movements. These architectures, for the first time, provide a computational basis for the flexible coupling between eye and hand movements.
- Short-latency allocentric control of saccadic eye movements
We found that the saccade end point was shifted from the actual target position toward the direction expected from allocentric coding when a large frame in the background was transiently shifted during the period of target presentation. The effect occurred within 150 ms. The present study provides direct evidence that the brain rapidly uses allocentric coding of a target to control immediate saccades.
- Go-activation endures following the presentation of a stop-signal: evidence from startle
In this study, a startling acoustic stimulus (SAS) was used to determine whether response outcome could be manipulated in a stop-signal task. Results revealed that presenting a SAS during stop-signal trials led to an increase in probability of responding even when presented 200 ms following the stop-signal. The latency of SAS responses indicates that go-activation remains accessible and modifiable well after the response is voluntarily inhibited, providing evidence against an irrevocable commitment to inhibition.
- Individual differences in implicit motor learning: task specificity in sensorimotor adaptation and sequence learning
We investigated individual differences in the ability to implicitly learn motor skills. As a prerequisite, we assessed whether individual differences were reliable across test sessions. We found that two commonly used tasks of implicit learning, visuomotor adaptation and the alternating serial reaction time task, exhibited good test-retest reliability in measures of learning and performance. However, the learning measures did not correlate between the two tasks, arguing against a shared process for implicit motor learning.
- Right prefrontal cortex transcranial direct current stimulation enhances multi-day savings in sensorimotor adaptation
We have previously reported that visuospatial working memory performance and magnitude of activation in the right dorsolateral prefrontal cortex predict the rate of manual visuomotor adaptation. Sensorimotor savings, or faster adaptation to a previously experienced perturbation, has been recently linked to cognitive processes. We show that facilitating the right prefrontal cortex with anodal transcranial direct current stimulation enhances sensorimotor savings compared with sham stimulation.
- High-frequency neuromuscular electrical stimulation modulates interhemispheric inhibition in healthy humans
High-frequency neuromuscular electrical stimulation (HF NMES) induces muscular contractions that partially match physiological motor control. Here, we tested whether HF NMES applied to the upper limb influences interhemispheric inhibition. Our results show that interhemispheric inhibition was increased after HF NMES and that this increase was correlated to the electromyographic activity within the contralateral homologous muscle. This opens up original perspectives for the implementation of HF NMES in sport training and neurorehabilitation.
RESEARCH ARTICLE | Glial Cells and Neuronal Signaling
- The acute inhibition of enteric glial metabolism with fluoroacetate alters calcium signaling, hemichannel function, and the expression of key proteins
Our study shows that the acute impairment of enteric glial metabolism with fluoroacetate (FA) alters specific glial functions that are associated with the modification of neurotransmission in the gut. These include subtle changes to glial agonist-evoked calcium signaling, the subsequent disruption of connexin-43 hemichannels, and changes in protein expression that are consistent with a transition to reactive glia. These changes in glial function offer a mechanistic explanation for the effects of FA on peripheral neuronal networks.
RESEARCH ARTICLES | Higher Neural Functions and Behavior
- Seeing a straight line on a curved surface: decoupling of patterns from surfaces by single IT neurons
We have no difficulty seeing a straight line on a curved piece of paper, but in fact, doing so requires decoupling the shape of the surface from the pattern itself. Here we report a novel form of invariance in the visual cortex: single neurons in monkey inferior temporal cortex respond similarly to congruent transformations of patterns and surfaces, in effect decoupling patterns from the surface on which they are overlaid.
- Temporal coordination of olfactory cortex sharp-wave activity with up- and downstates in the orbitofrontal cortex during slow-wave sleep
Simultaneous recordings of local field potentials and spike activities in the anterior piriform cortex (APC) and orbitofrontal cortex (OFC) during slow-wave sleep showed that APC sharp waves tended to occur during two distinct phases of OFC upstate: early phase, shortly after the down-to-up transition, and late phase, shortly before the up-to-down transition, suggesting that during slow-wave sleep, olfactory cortex and OFC areas communicate preferentially in the specific time windows.
- Independent coding of absolute duration and distance magnitudes in the prefrontal cortex
Human behavioral studies have shown that spatial and duration judgments can interfere with each other. We investigated the neural representation of such magnitudes in the prefrontal cortex. We found that the two magnitudes are independently coded by prefrontal neurons. We suggest that the interference among magnitude judgments might depend on the goal rather than the perceptual resource sharing.
- The relationship between ERP components and EEG spatial complexity in a visual Go/Nogo task
The reaction times, the latencies/amplitudes of event-related potential (ERP) components, the Go/Nogo N2 effect, and the Go/Nogo P3 effect are linked to the electroencephalographic (EEG) spatial complexity level. The EEG spatial complexity is closely related to demands of certain cognitive processes and could reflect the neural processing efficiency of human brain. Obtaining the single-trial ERP features through single-trial spatial complexity may be a more efficient approach than traditional methods.
- Role of human premotor dorsal region in learning a conditional visuomotor task
Conditional learning involves stimulus identification, motor response selection, response monitoring, memory encoding, and recall of the learned association. Premotor dorsal (PMd) has been implicated for conditional learning. However, the extent to which PMd might be involved in specific or all stages of conditional learning is not well understood. The novel finding of our study is that PMd appears to be involved with monitoring motor responses, a sensorimotor integration stage essential for conditional learning.
RESEARCH ARTICLES | Nervous System Pathophysiology
- Modulation of activity and conduction in single dorsal column axons by kilohertz-frequency spinal cord stimulation
Kilohertz-frequency spinal cord stimulation (KHF-SCS) is a new mode of SCS that may offer better pain relief than conventional SCS. However, the mechanism of action is poorly characterized, especially the effects of stimulation on dorsal column (DC) axons, which are the primary target of stimulation. This study provides the first recordings of single DC axons during KHF-SCS to quantify DC activity that has the potential to mediate the analgesic effects of KHF-SCS.
- Caveolin-1 regulation of disrupted-in-schizophrenia-1 as a potential therapeutic target for schizophrenia
The present study is the first to demonstrate that caveolin-1 can regulate DISC1 expression in neuronal models. Furthermore, the findings are consistent across three separate neuronal models that include rodent neurons (in vitro and in vivo) and human differentiated neurons derived from induced pluripotent stem cells. These findings justify further investigation regarding the modulatory role by caveolin on synaptic function and as a potential therapeutic target for the treatment of schizophrenia.
RESEARCH ARTICLES | Neural Circuits
- Thalamic state control of cortical paired-pulse dynamics
For the first time, we have been able to utilize optogenetic modulation of thalamic firing modes combined with optical imaging of cortex in the rat vibrissa system to directly test the role of thalamic state in shaping cortical response properties.
- Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury
In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the experimental results. Thus, after disruption of long-axon projections from RS neurons in the lamprey, descending propriospinal (PS) neurons appear to be a viable compensatory mechanism for indirect activation of spinal locomotor networks.
- Effects of ion channel noise on neural circuits: an application to the respiratory pattern generator to investigate breathing variability
A major source of noise in neuronal circuits is the “flickering” of ion currents passing through the neurons' membranes (channel noise), which cannot be suppressed experimentally. Computational simulations are therefore the best way to investigate the effects of this physiological noise by manipulating its level at will. We investigate the role of noise in the respiratory pattern generator and show that endogenous, breath-to-breath variability is tightly linked to the respiratory pattern.
RESEARCH ARTICLES | Sensory Processing
- Whisker row deprivation affects the flow of sensory information through rat barrel cortex
Sensory cortical plasticity is usually quantified by changes in evoked firing rate. In this study we quantified plasticity by changes in sensory detection performance using Chernoff information and receiver operating characteristic analysis. We found that whisker deprivation causes a change in information flow within the cortical layers and that layer 5 regular-spiking cells, despite showing only a small potentiation of short-latency input, show the greatest increase in information content for the spared input partly by decreasing their spontaneous activity.
- Innocuous warming enhances peripheral serotonergic itch signaling and evokes enhanced responses in serotonin-responsive dorsal horn neurons in the mouse
Skin warming often exacerbates itch in patients with itchy dermatitis. We demonstrate that warming the skin enhanced serotonin-evoked, but not histamine-evoked, itch behavior and responses of sensory dorsal root ganglion cells. Moreover, serotonin, but not histamine, enhanced responses of superficial dorsal horn neurons to innocuous warming. The results suggest that skin warming selectively enhances the responses of serotonin-sensitive pruriceptors, leading to increased firing of serotonin-sensitive dorsal horn neurons that signal nonhistaminergic itch.
- Stimulus context alters neural representations of faces in inferotemporal cortex
Neurons in inferotemporal (IT) cortex anticipate the arrival of a predictable stimulus, and visual responses to an expected stimulus are more distributed throughout the population of IT neurons, providing an enhanced representation of second-order stimulus information (in this case, viewing angle). The findings reveal a potential neural basis for the behavioral benefits of contextual expectation.
- Visual search for object categories is predicted by the representational architecture of high-level visual cortex
Here, we ask which neural regions have neural response patterns that correlate with behavioral performance in a visual processing task. We found that the representational structure across all of high-level visual cortex has the requisite structure to predict behavior. Furthermore, when directly comparing different neural regions, we found that they all had highly similar category-level representational structures. These results point to a ubiquitous and uniform representational structure in high-level visual cortex underlying visual object processing.
RESEARCH ARTICLES | Spinal Control of Motor Outputs
- Contractile function and motor unit firing rates of the human hamstrings
We studied motor unit firing rates (MUFRs) at various voluntary contraction intensities in the hamstrings, one of the only major lower limb muscles to have MUFRs affected by muscle length changes. Within the hamstrings muscle-specific differences have greater impact on MUFRs than length changes, with the biceps femoris having reduced neural drive compared with the semimembranosus-semimembranosus. Comparing our results to other lower limb muscles, flexors have inherently higher firing rate compared with extensors.
- Psychosocial stress alters the strength of reticulospinal input to the human upper trapezius
This study is the first to quantify stress-evoked changes in the acoustic startle reflex in the upper trapezius muscle of humans, and our findings reveal a complex pattern of inhibitory and facilitatory responses consistent with observations in nonhuman primates. We further demonstrate that psychosocial stress consistently reduces the amplitude of these responses. These findings have implications for the control of motor behaviors in response to stress.
- A novel computational model to probe visual search deficits during motor performance
Visual search has traditionally been studied in cognitive and perceptual paradigms, but little is known about how it contributes to visuomotor performance. We have developed a novel computational model to examine how three underlying processes of visual search (spatial planning, working memory, and peripheral visual processing) contribute to visual search during a visuomotor task. We show that deficits integrating spatial planning and working memory underlie abnormal performance in stroke survivors with frontoparietal damage.
- Overlap of movement planning and movement execution reduces reaction time
In the planning of a movement, the brain has the opportunity to delay the incorporation of accuracy requirements of the motor plan in order to reduce the reaction time by up to 100 ms (average: 32 ms). Such shortening of reaction time is observed here when the first phase of the movement consists of a transport phase. This forces us to reconsider the hypothesis that motor plans are fully defined before movement onset.
- Rapid and lasting enhancement of dopaminergic modulation at the hippocampal mossy fiber synapse by electroconvulsive treatment
We show that electroconvulsive therapy (ECT)-like stimulation greatly enhances synaptic potentiation induced by dopamine at the excitatory synapse formed by the hippocampal mossy fiber in mice. The effect of ECT-like stimulation on the dopaminergic modulation was rapidly induced, maintained for more than 4 wk after repeated treatments, and most likely mediated by increased expression of the dopamine D1 receptor. These effects may be relevant to fast-acting strong antidepressant action of ECT.