Crosstalk between inhibitory and excitatory neurotransmitter systems during synapse development in the brain

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Synapses are key sites of neuronal communication in the brain. They are highly specialized structures with complex molecular machinery that enables the process of chemical neurotransmission to occur. Recent evidence suggests that early signaling through the neurotransmitter GABA, may serve to sculpt brain connectivity. However, the molecular and cellular events that underlie this process remain poorly understood. In this Discovery Grant proposal, we will confront several unresolved issues with respect to the function of early GABA signaling and its role in regulating synaptic connectivity. First, we will determine how early GABA transmission controls glutamate synapse formation using advanced molecular manipulations, high resolution confocal microscopy, and electrophysiology techniques. Our preliminary data suggests that early signaling through the neurotransmitter GABA controls the number of excitatory synapses on developing hippocampal neurons. Next, we will monitor the development of GABA synapses on neurons and define their relationship to developing glutamate synapses. Finally, we will investigate the molecular and cellular processes that govern early GABA signaling. This Discovery Grant project will provide excellent conceptual and technical training for students interested in understanding the development of brain circuitry. The data produced by these students will also create novel insight into mechanisms that control the process of synapse formation.