Function of Neocortical GABAergic Interneurons in Local Circuit Activations

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DESCRIPTION (provided by applicant): GABAergic interneurons, which are implicated in many disease states, form a small but crucial population of cortical neurons. Attempts to classify the vast array of interneurons in mammalian cortex have shed light on many of their basic properties, but very little is known about the function of distinct classes of interneurons in neuronal networks. While it has been shown GABAergic interneurons can affect the function of large brain areas, it is not known how they do so. The studies proposed here are aimed at elucidating the function of neocortical interneurons within the context of circuit activations. These activations, during which neurons are synchronously depolarized and fire action potentials, show spatio-temporal stereotypy and have been associated with important neural functions. GABAergic interneurons, which are thought to be important for controlling the output of excitatory cells, participate during circuit activations, but their exact role is unknown. This application, using cutting edge optical techniques, will focus on investigating how interneurons affect neuronal activity in local circuits. Specifically I will test the hypothesis that specific subclasses of interneurons are crucial for determining distinct features of cortical circuit activations. Using transgenic mouse lines in which subsets of GABAergic interneurons are labeled with GFP, I will decrease or increase the activity of target interneurons using three approaches: 1) whole cell patch clamping, 2) two photon laser ablation and 3) one/two photon uncaging of either excitatory or inhibitory neurotransmitters. PUBLIC HEALTH RELEVANCE: Since altered function of inhibitory neurons is thought to underlie a number of neurological disorders, including schizophrenia and epilepsy, the changes I observe in circuit activations may reflect the underlying network pathologies associated with these conditions.