Cerebral cortex
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Traumatic brain injury (TBI) is a major risk factor for developing pharmaco-resistant epilepsy. Although disruptions in brain circuitry are associated with TBI, the precise mechanisms by which brain injury leads to epileptiform network activity is unknown. Using controlled cortical impact (CCI) as a model of TBI, we examined how cortical excitability and glutamatergic signaling was altered following injury. ⋯ Lastly, spontaneous inhibitory postsynaptic current frequency decreased and spontaneous excitatory postsynaptic current increased after CCI injury. Our results suggest that specific cortical neuronal microcircuits may initiate and facilitate the spread of epileptiform activity following TBI. Increased glutamatergic signaling due to loss of GABAergic control may provide a mechanism by which TBI can give rise to post-traumatic epilepsy.
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The long-term depression (LTD)-like changes in human primary motor cortex (M1) excitability induced by continuous theta burst stimulation (cTBS) are subject to reversal (i.e., de-depression) following behavioral engagement of M1, limiting its therapeutic potential under behaviorally relevant conditions. Experiments in animals suggest that the repeated, spaced application of stimulation trains may consolidate synaptic plasticity, making it resistant to reversal by physiological activity. Although there is evidence that repeated cTBS prolongs LTD-like M1 neuroplasticity in humans, whether these effects are resistant to de-depression has not been tested. ⋯ While the LTD-like MEP depression induced by a single cTBS was abolished by subsequent voluntary contraction, paired cTBS induced MEP depression that was resistant to reversal. This MEP depression was also resistant to reversal when an experimental de-depression protocol was used instead of a voluntary contraction. Our findings suggest that repeated cTBS applications consolidate LTD-like M1 neuroplasticity, which may have important implications for the clinical application of cTBS.
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It has been established that bimanual coordination with augmented feedback (FB) versus no augmented feedback (NFB) is associated with activity in different brain regions. It is unclear however, whether this distinction remains after practice comprising both these conditions. Functional magnetic resonance imaging was used in humans to compare visual FB versus NFB conditions for a bimanual tracking task, and their differential evolution across learning. ⋯ Activations at the whole-brain level initially differed for FB versus NFB movements but this differentiation diminished with training for the movement execution phase. Specifically, in right dorsal premotor cortex and right dorsolateral prefrontal cortex activation increased for NFB and decreased for FB trials to converge toward the end of practice. This suggests that learning led to a decreased need to adjust the ongoing movement on the basis of FB, whereas online monitoring became more pronounced in NFB trials as discrepancies between the required and the produced motor output were detected more accurately after training, due to a generic internal reference of correctness supporting movement control under varying conditions.
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Dendritic protrusions (spines and filopodia) are structural indicators of synapses that have been linked to neuronal learning and memory through their morphological alterations induced by development and experienced-dependent activities. Although previous studies have demonstrated that depriving sensory experience leads to structural changes in neocortical organization, the more subtle effects on dendritic protrusions remain unclear, mostly due to focus on only one specific cell type and/or age of manipulation. Here, we show that sensory deprivation induced by whisker trimming influences the dendritic protrusions of basilar dendrites located in thalamocortical recipient lamina (IV and VI) of the mouse barrel cortex in a layer-specific manner. ⋯ In addition, chronic pharmacological blockade of N-methyl-d-aspartate receptors (NMDARs) increased protrusion density in both layers IV and VI, which returned to the control level after 1 month of drug withdrawal. Our data reveal that different cortical layers respond to chronic sensory deprivation in different ways, with more pronounced effects during developmental critical periods than adulthood. We also show that chronically blocking NMDARs activity during developmental critical period also influences the protrusion density and morphology in the cerebral cortex.
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Although the thalamus is believed to regulate and coordinate cortical activity both within and across functional regions, such as motor and visual cortices, direct evidence for such regulation and the mechanism of regulation remains poorly described. Using simultaneous invasive recordings of cortical and thalamic electrophysiological activity in 2 awake and spontaneously behaving human subjects, we provide direct evidence of thalamic regulation of cortical activity through a mechanism of phase-amplitude coupling (PAC), in which the phase of low frequency oscillations regulates the amplitude of higher frequency oscillations. ⋯ This relationship allows for new evidence of thalamocortical PAC. Given the diffuse connectivity of the thalamus with the cerebral cortex, thalamocortical PAC may play an important role in addressing the binding problem, including both integration and segregation of information within and across cortical areas.