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Adaptation of neural responses due to the history of sensory input has been observed across all sensory modalities. However, the computational role of adaptation is not fully understood, especially when one considers neural coding problems in which adaptation increases the ambiguity of the neural responses to simple stimuli. To address this, we quantified the impact of adaptation on the information conveyed by thalamic neurons about paired whisker stimuli in male rat. At the single neuron level, although paired-pulse adaptation reduces the information about the present stimulus, the information per spike increases. Moreover, the adapted response can convey significant amounts of information about whether, when and where a previous stimulus occurred. At the population level, ambiguity of the adapted responses about the present stimulus can be compensated for by large numbers of neurons. Therefore, paired-pulse adaptation does not reduce the discriminability of simple stimuli. It provides information about the spatiotemporal context of stimulus history. SIGNIFICANCE STATEMENT The present work provides a computational framework that demonstrates how adaptation allows neurons to encode spatiotemporal dynamics of stimulus history., (Copyright © 2017 the authors 0270-6474/17/3710012-10$15.00/0.)

During cortical development, plasticity reflects the dynamic equilibrium between increasing and decreasing functional connectivity subserved by synaptic sprouting and pruning. After adult cortical deafferentation, plasticity seems to be dominated by increased functional connectivity, leading to the classical expansive reorganization from the intact to the deafferented cortex. In contrast, here we show a striking "decrease" in the fast cortical responses to high-intensity forepaw stimulation 1-3 months after complete thoracic spinal cord transection, as evident in both local field potentials and intracellular in vivo recordings. Importantly, this decrease in fast cortical responses co-exists with an "increase" in cortical activation over slower post-stimulus timescales, as measured by an increased forepaw-to-hindpaw propagation of stimulus-triggered cortical up-states, as well as by the enhanced slow sustained depolarization evoked by high-frequency forepaw stimuli in the deafferented hindpaw cortex. This coincidence of diminished fast cortical responses and enhanced slow cortical activation offers a dual perspective of adult cortical plasticity after spinal cord injury., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The field of invasive brain-machine interfaces (BMIs) is typically associated with neuroprosthetic applications aiming to recover loss of motor function. However, BMIs also represent a powerful tool to address fundamental questions in neuroscience. The observed subjects of BMI experiments can also be considered as indirect observers of their own neurophysiological activity, and the relationship between observed neurons and (artificial) behavior can be genuinely causal rather than indirectly correlative. These two characteristics defy the classical object-observer duality, making BMIs particularly appealing for investigating how information is encoded and decoded by neural circuits in real time, how this coding changes with physiological learning and plasticity, and how it is altered in pathological conditions. Within neuroengineering, BMI is like a tree that opens its branches into many traditional engineering fields, but also extends deep roots into basic neuroscience beyond neuroprosthetics., (Copyright © 2015 Elsevier Inc. All rights reserved.)

From the perspective of neural coding, the considerable trial-to-trial variability in the responses of neurons to sensory stimuli is puzzling. Trial-to-trial response variability is typically interpreted in terms of "noise" (i.e., it represents either intrinsic noise of the system or information unrelated to the stimuli). However, trial-to-trial response variability can be considerably different across stimuli, suggesting that it could also provide an important contribution to the information conveyed by the neural responses about the stimuli. To test this hypothesis, we addressed the problem of discriminating stimulus location from the spike-count responses of neurons recorded in the ventro-postero-medial (VPM) nucleus of the thalamus in anesthetized rats. Using a recently developed information theory approach, we verified that differences between stimuli in the trial-to-trial spike-count variability of the responses provided an important contribution to the overall information carried by the neurons. In addition, we found that the relatively reliable (sub-Poisson) firing regime of our VPM neurons was not only more informative, but also more redundant between neurons compared with a more variable (Poisson) firing regime with the same total number of spikes. The typical increase in trial-to-trial response variability from the periphery to the cortex could therefore serve as a strategy to reduce redundancy between neurons and promote efficient sparse coding distributed in large populations of neurons. Overall, our data suggest that the trial-to-trial response variability plays a critical role in establishing the trade-off between total information and redundancy between neurons in population codes.

Deep brain stimulation (DBS) of the ventralis oralis (VO) complex of the thalamus improves tics in patients with Tourette syndrome (TS). To neurophysiologically describe the VO complex we recorded, in seven patients with TS undergoing DBS electrode implantation, single-unit activity during surgery and local field potentials (LFPs) a few days after surgery. Single unit recordings showed that the VO complex is characterized by a localized pattern of bursting neuronal activity. LFP spectra demonstrated that VO of TS patients has a prominent oscillatory activity at low frequencies (2-7 Hz) and in the alpha-band (8-13 Hz), and a virtually absent beta activity. In each patient, the main LFP frequency significantly correlated with single-unit interburst frequency. In conclusion, we observed an oscillatory bursting activity in the VO as target region in patients with severe TS undergoing DBS surgery., ((c) 2010 Movement Disorder Society.)

Computational studies are challenging the intuitive view that neurons with broad tuning curves are necessarily less discriminative than neurons with sharp tuning curves. In the context of somatosensory processing, broad tuning curves are equivalent to large receptive fields. To clarify the computational role of large receptive fields for cortical processing of somatosensory information, we recorded ensembles of single neurons from the infragranular forelimb/forepaw region of the rat primary somatosensory cortex while tactile stimuli were separately delivered to different locations on the forelimbs/forepaws under light anesthesia. We specifically adopted the perspective of individual columns/segregates receiving inputs from multiple body location. Using single-trial analyses of many single-neuron responses, we obtained two main results. 1) The responses of even small populations of neurons recorded from within the same estimated column/segregate can be used to discriminate between stimuli delivered to different surround locations in the excitatory receptive fields. 2) The temporal precision of surround responses is sufficiently high for spike timing to add information over spike count in the discrimination between surround locations. This surround spike-timing code (i) is particularly informative when spike count is ambiguous, e.g., in the discrimination between close locations or when receptive fields are large, (ii) becomes progressively more informative as the number of neurons increases, (iii) is a first-spike code, and (iv) is not limited by the assumption that the time of stimulus onset is known. These results suggest that even though large receptive fields result in a loss of spatial selectivity of single neurons, they can provide as a counterpart a sophisticated temporal code based on latency differences in large populations of neurons without necessarily sacrificing basic information about stimulus location.

Ripples are sharp-wave-associated field oscillations (100-300 Hz) recorded in the hippocampus during behavioral immobility and slow-wave sleep. In epileptic rats and humans, a different and faster oscillation (200-600 Hz), termed fast ripples, has been described. However, the basic mechanisms are unknown. Here, we propose that fast ripples emerge from a disorganized ripple pattern caused by unreliable firing in the epileptic hippocampus. Enhanced synaptic activity is responsible for the irregular bursting of CA3 pyramidal cells due to large membrane potential fluctuations. Lower field interactions and a reduced spike-timing reliability concur with decreased spatial synchronization and the emergence of fast ripples. Reducing synaptically driven membrane potential fluctuations improves both spike-timing reliability and spatial synchronization and restores ripples in the epileptic hippocampus. Conversely, a lower spike-timing reliability, with reduced potassium currents, is associated with ripple shuffling in normal hippocampus. Therefore, fast ripples may reflect a pathological desynchronization of the normal ripple pattern.

The problem of understanding how ensembles of neurons code for somatosensory information has been defined as a classification problem: given the response of a population of neurons to a set of stimuli, which stimulus generated the response on a single-trial basis? Multivariate statistical techniques such as linear discriminant analysis (LDA) and artificial neural networks (ANNs), and different types of preprocessing stages, such as principal and independent component analysis, have been used to solve this classification problem, with surprisingly small performance differences. Therefore, the goal of this project was to design a new method to maximize computational efficiency rather than classification performance. We developed a peri-stimulus time histogram (PSTH)-based method, which consists of creating a set of templates based on the average neural responses to stimuli and classifying each single trial by assigning it to the stimulus with the 'closest' template in the Euclidean distance sense. The PSTH-based method is computationally more efficient than methods as simple as linear discriminant analysis, performs significantly better than discriminant analyses (linear, quadratic or Mahalanobis) when small binsizes are used (1 ms) and as well as LDA with any other binsize, is optimal among other minimum-distance classifiers and can be optimally applied on raw neural data without a previous stage of dimension reduction. We conclude that the PSTH-based method is an efficient alternative to more sophisticated methods such as LDA and ANNs to study how ensemble of neurons code for discrete sensory stimuli, especially when datasets with many variables are used and when the time resolution of the neural code is one of the factors of interest.

BackgroundIn rat models of spinal cord injury, at least 3 different strategies can be used to promote long-term cortical reorganization: (1) active exercise above the level of the lesion; (2) passive exercise below the level of the lesion; and (3) serotonergic pharmacotherapy. Whether and how these potential therapeutic strategies-and their underlying mechanisms of action-interact remains unknown. Methods In spinally transected adult rats, we compared the effects of active exercise above the level of the lesion (treadmill), passive exercise below the level of the lesion (bike), serotonergic pharmacotherapy (quipazine), and combinations of the above therapies (bike+quipazine, treadmill+quipazine, bike+treadmill+quipazine) on long-term cortical reorganization (9 weeks after the spinal transection). Cortical reorganization was measured as the percentage of cells recorded in the deafferented hindlimb cortex that responded to tactile stimulation of the contralateral forelimb. Results Bike and quipazine are "competing" therapies for cortical reorganization, in the sense that quipazine limits the cortical reorganization induced by bike, whereas treadmill and quipazine are "collaborative" therapies, in the sense that the reorganization induced by quipazine combined with treadmill is greater than the reorganization induced by either quipazine or treadmill.ConclusionsThese results uncover the interactive effects between active/passive exercise and serotonergic pharmacotherapy on cortical reorganization after spinal cord injury, emphasizing the importance of understanding the effects of therapeutic strategies in spinal cord injury (and in other forms of deafferentation) from an integrated system-level approach.

Physical exercise promotes neural plasticity in the brain of healthy subjects and modulates pathophysiological neural plasticity after sensorimotor loss, but the mechanisms of this action are not fully understood. After spinal cord injury, cortical reorganization can be maximized by exercising the non-affected body or the residual functions of the affected body. However, exercise per se also produces systemic changes - such as increased cardiovascular fitness, improved circulation and neuroendocrine changes - that have a great impact on brain function and plasticity. It is therefore possible that passive exercise therapies typically applied below the level of the lesion in patients with spinal cord injury could put the brain in a more plastic state and promote cortical reorganization. To directly test this hypothesis, we applied passive hindlimb bike exercise after complete thoracic transection of the spinal cord in adult rats. Using western blot analysis, we found that the level of proteins associated with plasticity - specifically ADCY1 and BDNF - increased in the somatosensory cortex of transected animals that received passive bike exercise compared to transected animals that received sham exercise. Using electrophysiological techniques, we then verified that neurons in the deafferented hindlimb cortex increased their responsiveness to tactile stimuli delivered to the forelimb in transected animals that received passive bike exercise compared to transected animals that received sham exercise. Passive exercise below the level of the lesion, therefore, promotes cortical reorganization after spinal cord injury, uncovering a brain-body interaction that does not rely on intact sensorimotor pathways connecting the exercised body parts and the brain.

Adaptation of neural responses due to the history of sensory input has been observed across all sensory modalities. However, the computational role of adaptation is not fully understood, especially when one considers neural coding problems in which adaptation increases the ambiguity of the neural responses to simple stimuli. To address this, we quantified the impact of adaptation on the information conveyed by thalamic neurons about paired whisker stimuli in male rat. At the single neuron level, although paired-pulse adaptation reduces the information about the present stimulus, the information per spike increases. Moreover, the adapted response can convey significant amounts of information about whether, when and where a previous stimulus occurred. At the population level, ambiguity of the adapted responses about the present stimulus can be compensated for by large numbers of neurons. Therefore, paired-pulse adaptation does not reduce the discriminability of simple stimuli. It provides information about the spatiotemporal context of stimulus history. [ABSTRACT FROM AUTHOR]

The aim of this study was to test the hypothesis that the significance of spike timing in somatosensory processing is not a specific feature of the whisker cortex but a more general characteristic of the primary somatosensory cortex. We recorded ensembles of neurons using microwire arrays implanted in the deep layers of the forelimb region of the rat primary somatosensory cortex in response to step stimuli delivered to the cutaneous surface of the contralateral body. We used a recently developed peristimulus time histogram (PSTH)-based classification method to investigate the temporal precision of the code by evaluating how changing the bin size (from 40 to 1 msec) would affect the ability of the ensemble responses to discriminate stimulus location on a single-trial basis. The information related to the discrimination was redundantly distributed within the ensembles, and the ability to discriminate stimulus location increased when decreasing the bin size, reaching a maximum at 4 msec. In our experiment, at 4 msec bin size the first spike per neuron after the stimulus conveyed almost as much information as the entire responses, so the temporal precision of the code was preserved in the first spikes. Subsequent spikes were less frequent but conveyed more information per spike. Finally, not only the trials correctly classified but also the trials incorrectly classified conveyed information about stimulus location with a similar temporal precision. We conclude that the role of spike timing in cortical somatosensory processing is not an exclusive feature of the highly specialized rat trigeminal system, but a more general property of the rat primary somatosensory cortex. [ABSTRACT FROM AUTHOR]