Grant: Operating Grant

Normal brain function relies on a balance between excitation and inhibition of neurons. Disruption of this balance is involved in several neuropsychiatric disorders including autism, schizophrenia, and attention deficit hyperactive disorder as well as epilepsy. Excitation or inhibition occurs at connections between neurons called synapses. At these structures, neurons release either excitatory (glutamate) or inhibitory (GABA) substances that are received by the target neurons. Recent studies have revealed many neuronal adhesion mechanisms that regulate the development of excitatory synapses. Yet, very little is known about adhesion mechanisms underlying inhibitory synapse development. In preliminary studies, we recently identified a novel adhesion molecule that induces inhibitory synapse development. In this proposal, we aim to characterize the roles of this new adhesion molecule in inhibitory synapse development and brain activity by using cellular, molecular, electrophysiological, and genetic approaches. Many cell adhesion molecules with synapse-inducing activity are genetically linked with neuropsychiatric disorders. In addition, chromosomal deletion overlapping with the gene for our novel synapse-inducing molecule is associated with mental retardation and epilepsy. Our study will therefore provide important insights into the pathogenesis of neuropsychiatric disorders with excitation/inhibition imbalance and help to develop new therapeutic strategies to normalize this imbalance.