Synchronization in Primate Cerebellar Granule Cell Layer Local Field Potentials: Basic Anisotropy and Dynamic Changes During Active Expectancy

The cerebellar cortex is remarkable for its organizational regularity, out of which task-related neural networks should emerge. In Purkinje cells, both complex and simple spike network patterns are evident in sensorimotor behavior. However, task-related patterns of activity in the granule cell layer (GCL) have been less studied. We recorded local field potential (LFP) activity simultaneously in pairs of GCL sites in monkeys performing an active expectancy (lever-press) task, in passive expectancy, and at rest. LFP sites were selected when they showed strong 10–25 Hz oscillations; pair orientation was in stereotaxic sagittal and coronal (mainly), and diagonal. As shown previously, LFP oscillations at each site were modulated during the lever-press task. Synchronization across LFP pairs showed an evident basic anisotropy at rest: sagittal pairs of LFPs were better synchronized (more than double the cross-correlation coefficients) than coronal pairs, and more than diagonal pairs. On the other hand, this basic anisotropy was modifiable: during the active expectancy condition, where sagittal and coronal orientations were tested, synchronization of LFP pairs would increase just preceding movement, most notably for the coronal pairs. This lateral extension of synchronization was not observed in passive expectancy. The basic pattern of synchronization at rest, favoring sagittal synchrony, thus seemed to adapt in a dynamic fashion, potentially extending laterally to include more cerebellar cortex elements. This dynamic anisotropy in LFP synchronization could underlie GCL network organization in the context of sensorimotor tasks

Perceptual plasticity in damaged adult visual systems

AbstractPlasticity appears to be a ubiquitous property of nervous systems, regardless of developmental stage or complexity. In the visual system of higher mammals, perceptual plasticity has been intensively studied, both during development and in adulthood. However, the last few years have seen some significant controversies arise about the existence and properties of visual plasticity after permanent damage to the adult visual system. The study of perceptual plasticity in damaged, adult visual systems is of interest for several reasons. First, it is an important means of unmasking the relative contribution of individual visual areas to visual learning, adaptation and priming, among other plastic phenomena. Second, it can provide knowledge that is essential for the development of effective therapies to rehabilitate the increasing number of people who suffer the functional consequences of damage at different levels of their visual hierarchy. This review summarizes the available evidence on the subject and proposes that visual plasticity may be just as ubiquitous after damage as it is in the intact visual system. However, damage may alter visual plasticity in ways that are still being defined

Targeted cortical reorganization using optogenetics in non-human primates.

Brain stimulation modulates the excitability of neural circuits and drives neuroplasticity. While the local effects of stimulation have been an active area of investigation, the effects on large-scale networks remain largely unexplored. We studied stimulation-induced changes in network dynamics in two macaques. A large-scale optogenetic interface enabled simultaneous stimulation of excitatory neurons and electrocorticographic recording across primary somatosensory (S1) and motor (M1) cortex (Yazdan-Shahmorad et al., 2016). We tracked two measures of network connectivity, the network response to focal stimulation and the baseline coherence between pairs of electrodes; these were strongly correlated before stimulation. Within minutes, stimulation in S1 or M1 significantly strengthened the gross functional connectivity between these areas. At a finer scale, stimulation led to heterogeneous connectivity changes across the network. These changes reflected the correlations introduced by stimulation-evoked activity, consistent with Hebbian plasticity models. This work extends Hebbian plasticity models to large-scale circuits, with significant implications for stimulation-based neurorehabilitation

Unique Features and Neuronal Properties in a Multisensory Cortex

UNIQUE FEAUTRES OF ORGANIZATION AND NEURONAL PROPERTIES IN A MULTISENSORY CORTEX Multisensory processing is a ubiquitous sensory effect that underlies a wide variety of behaviors, such as detection and orientation, as well as perceptual phenomena from speech comprehension to binding. Such multisensory perceptual effects are presumed to be based in cortex, especially within areas known to contain multisensory neurons. However, unlike their lower-level/primary sensory cortical counterparts, little is known about the connectional, functional and laminar organization of higher-level multisensory cortex. Therefore, to examine the fundamental features of neuronal processing and organization in the multisensory cortical area of the posterior parietal cortex (PPr) of ferrets, the present experiments utilized a combination of immunohistological, neuroanatomical and multiple single-channel electrophysiological recording techniques. These experiments produced four main results. First, convergence of extrinsic inputs from unisensory cortical areas predominantly in layers 2-3 in PPr corresponded with the high proportion of multisensory neurons in those layers. This is consistent with multisensory responses in this higher-level multisensory region being driven by cortico-cortical, rather than thalamo-cortical connections. Second, the laminar organization of the PPr differed substantially from the pattern commonly observed in primary sensory cortices. The PPr has a reduced layer 4 compared to primary sensory cortices, which does not receive input from principal thalamic nuclei. Third, the distribution of unisensory and multisensory neurons and properties differs significantly by layer. Given the laminar-dependent input-output relationships, this suggests that unisensory and multisensory signals are processed in parallel as they pass through the circuitry of the PPr. Finally, specific functional properties of bimodal neurons differed significantly from those of their unisensory counterparts. Thus, despite their coextensive distribution within cortex, these results differentiate bimodal from unisensory neurons in ways that have never been examined before. Together these experiments represent the first combined anatomical-electrophysiological examination of the laminar organization of a multisensory cortex and the first systematic comparison of the functional properties of bimodal and unisensory neurons. These results are essential for understanding the neural bases of multisensory processing and carry significant implications for the accurate interpretation of macroscopic studies of multisensory brain regions (i.e. fMRI, EEG), because bimodal and unisensory neurons within a given neural region can no longer be assumed to respond similarly to a given external stimulus

The Critical Role of Golgi Cells in Regulating Spatio-Temporal Integration and Plasticity at the Cerebellum Input Stage

The discovery of the Golgi cell is bound to the foundation of the Neuron Doctrine. Recently, the excitable mechanisms of this inhibitory interneuron have been investigated with modern experimental and computational techniques raising renewed interest for the implications it might have for cerebellar circuit functions. Golgi cells are pacemakers with preferential response frequency and phase-reset in the theta-frequency band and can therefore impose specific temporal dynamics to granule cell responses. Moreover, through their connectivity, Golgi cells determine the spatio-temporal organization of cerebellar activity. Finally, Golgi cells, by controlling granule cell depolarization and NMDA channel unblock, regulate the induction of long-term synaptic plasticity at the mossy fiber – granule cell synapse. Thus, the Golgi cells can exert an extensive control on spatio-temporal signal organization and information storage in the granular layer playing a critical role for cerebellar computation

The Critical Role of Golgi Cells in Regulating Spatio-Temporal Integration and Plasticity at the Cerebellum Input Stage

The discovery of the Golgi cell is bound to the foundation of the Neuron Doctrine. Recently, the excitable mechanisms of this inhibitory interneuron have been investigated with modern experimental and computational techniques raising renewed interest for the implications it might have for cerebellar circuit functions. Golgi cells are pacemakers with preferential response frequency and phase-reset in the theta-frequency band and can therefore impose specific temporal dynamics to granule cell responses. Moreover, through their connectivity, Golgi cells determine the spatio-temporal organization of cerebellar activity. Finally, Golgi cells, by controlling granule cell depolarization and NMDA channel unblock, regulate the induction of long-term synaptic plasticity at the mossy fiber – granule cell synapse. Thus, the Golgi cells can exert an extensive control on spatio-temporal signal organization and information storage in the granular layer playing a critical role for cerebellar computation

Integrative functional genomic analysis of human brain development and neuropsychiatric risks

To broaden our understanding of human neurodevelopment, we profiled transcriptomic and epigenomic landscapes across brain regions and/or cell types for the entire span of prenatal and postnatal development. Integrative analysis revealed temporal, regional, sex, and cell type-specific dynamics.We observed a global transcriptomic cup-shaped pattern, characterized by a late fetal transition associated with sharply decreased regional differences and changes in cellular composition and maturation, followed by a reversal in childhood-adolescence, and accompanied by epigenomic reorganizations. Analysis of gene coexpression modules revealed relationships with epigenomic regulation and neurodevelopmental processes. Genes with genetic associations to brain-based traits and neuropsychiatric disorders (including MEF2C, SATB2, SOX5, TCF4, and TSHZ3) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks

Using the Gibbs Function as a Measure of Human Brain Development Trends from Fetal Stage to Advanced Age

We propose to use a Gibbs free energy function as a measure of the human brain development. We adopt this approach to the development of the human brain over the human lifespan: from a prenatal stage to advanced age. We used proteomic expression data with the Gibbs free energy to quantify human brain’s protein–protein interaction networks. The data, obtained from BioGRID, comprised tissue samples from the 16 main brain areas, at different ages, of 57 post-mortem human brains. We found a consistent functional dependence of the Gibbs free energies on age for most of the areas and both sexes. A significant upward trend in the Gibbs function was found during the fetal stages, which is followed by a sharp drop at birth with a subsequent period of relative stability and a final upward trend toward advanced age. We interpret these data in terms of structure formation followed by its stabilization and eventual deterioration. Furthermore, gender data analysis has uncovered the existence of functional differences, showing male Gibbs function values lower than female at prenatal and neonatal ages, which become higher at ages 8 to 40 and finally converging at late adulthood with the corresponding female Gibbs functions

Progress toward an understanding of cortical computation

The additional data, perspectives, questions, and criticisms contributed by the commentaries strengthen our view that local cortical processors coordinate their activity with the context in which it occurs using contextual fields and synchronized population codes. We therefore predict that whereas the specialization of function has been the keynote of this century the coordination of function will be the keynote of the next