Grant: Operating Grant

Brain development requires orchestrated formation of connections between nerve cells. These synaptic connections are the main units of communication in the brain, where chemical neurotransmitter signaling occurs. This research is about molecules that drive formation and organize the properties of nerve cell connections. The best-known triggers of nerve cell connections are proteins called neuroligin and neurexin. Binding of neuroligin on one nerve cell to neurexin on another nerve cell induces localized synaptic connection and neurotransmission. We recently identified novel signals that regulate the function of neuroligin, suppressing its ability to drive nerve cell connections. We will use a combination of molecular genetics, cell culture, fluorescence imaging, and electrophysiology to assess mechanisms of action of these novel regulators of neuroligin and to determine their role in brain development and function. Genetic variants in neurexin, neuroligin and their regulators increase risk of developing autism and schizophrenia. Thus, a goal of this research is to understand how these genetic alterations change brain chemistry and connectivity, and to develop more effective directed therapies for improving mental health.