The development of excitatory and inhibitory circuits in the neocortex is critical for establishing normal patterns of brain activity, and dysregulation of this process may contribute to a number of neuropsychiatric disorders, including schizophrenia and autism. However, the organization and regulation of inhibitory synaptogenesis during early development remain poorly understood. This lack of knowledge is due, in part, to heterogeneity in GABAergic circuits and the absence of appropriate tools for dissecting the contribution of different IN populations to early GABAergic signaling. In the present study, we utilize a combination to electrophysiology, optogenetics, 2-photon imaging and uncaging, and fluorescent labeling of GABAergic synapses to (1) elaborate the development of functional inhibitory inputs to pyramidal neuron (PN) dendrites, (2) reveal novel mechanisms for circuit-specific GABAergic plasticity, and (3) elucidate the interactions of glutamatergic and GABAergic signaling in the normal wiring of cortical circuits. Our overall goal is to understand the links between excitatory and inhibitory signaling that operate during development and maintain cortical circuit function. We expect that our results will generate new avenues for exploring both the cell biology of GABAergic function and the general mechanisms by which the brain develops and adapts to experience.

Public Health Relevance

This proposal seeks to understand the functional development of inhibitory GABAergic synapses in the prefrontal cortex. Results from these studies will help identify novel mechanisms by which the brain is wired during development and in response to experience. We further expect our findings to provide important insights into the cellular underpinnings of neurodevelopmental disorders such as autism and schizophrenia.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Kim, Douglas S
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Yale University
Schools of Medicine
New Haven
United States
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