Circuit Mechanisms of Cortical Synchronizations

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DESCRIPTION (provided by applicant): The proposed studies are aimed at elucidating the cellular mechanisms within cortex that lead to the generation of UP states. UP states are a distinct type of synchronous activation of neuronal ensembles in mammalian brain in which groups of neurons are synchronously depolarized for hundreds of milliseconds and fire action potentials during that time. They have been associated with neural function such a sensory input and motor output. As importantly, the ensemble of neurons participating in an UP state appears to be stable, in that the same local group of cells fires in the same sequence on repeated occasions. The stereotyped spatiotemporal dynamics of these neural ensembles suggest that they may arise from underlying neuronal connectivity patterns that are critical for their organization and function. However, much remains to be learned about how these UP states are triggered or maintained. This application tests the hypothesis that neurons that are members of UP state ensembles are themselves critical for triggering and maintaining their own synchronous depolarization. We propose a series of stimulation and ablation studies to test this hypothesis. Given the possibility that these neural ensembles likely represent modular elements critical in cortical function, their disruption may lead to disorganization of neural activity as is observed in a number of neurological disorders including epilepsy.