Role of Inhibitory Synapses in Shaping Excitatory Circuits

2020 Seed Grant
Won Chan Oh, Ph.D.
University of Colorado

How memories are encoded in the brain is a central question in neuroscience. Our capacity to learn and recall past events is of extreme importance and loss of this ability is a hallmark feature of numerous devastating neurological disorders such as Alzheimer’s disease. Synapses, the connections between neurons in the brain, are the fundamental units that are shaped when we learn. Importantly, two types of synapses, excitatory and inhibitory, have opposing effects on neurons, and a precise balance between these synapse types is essential for correct neuronal function during learning and memory. Communication between excitatory and inhibitory synapses is believed to be critical for maintaining this balance. This proposal addresses key questions of fundamental significance; 1) how are excitatory and inhibitory synapses balanced throughout brain development? And 2) what cellular and molecular signaling mechanisms underlie the communication between excitatory and inhibitory synapses during nervous system development and during learning? We will use advanced two-photon microscopy techniques, pharmacology, and electrophysiology to define how excitatory and inhibitory synapses are regulated during development of neural circuits. Our work will provide a powerful experimental framework for understanding how the brain achieves and maintains proper balance between excitatory and inhibitory synapses, and how this balance is altered in neuropsychiatric disorders.

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