A Novel Approach to Regulate Glutamate Signaling in Neuropsychiatric Disease
Glutamate is a chemical neurotransmitter that plays a critical role in facilitating synaptic communication between neurons and receptors in the brain. Normal brain processes, such as those that underlie cognition, emotion and behavior, all require that glutamate be released from a neuron in a regulated fashion. Dysfunction of glutamate is implicated in many neuropsychiatric disorders, including schizophrenia, epilepsy, and autism. While many drug development efforts have been aimed at altering glutamate receptor activity on the post-synaptic side, there has been little study into the mechanisms that control the release of glutamate on the pre-synaptic side. I propose to explore a new therapy to regulate glutamate release. My lab has already developed optical reporters that show a burst of light in the synapse when glutamate is released. We are now using this technology to explore modulators of glutamate release that may be novel therapeutic targets. In particular, we have discovered a novel pathway that regulates release of glutamate by a specific circuit of synapses under conditions of high activity. We hope that targeting this signaling system will allow us to dampen excess activity while allowing normal physiological transmission to proceed. Such normalization of glutamate signaling represents a promising new strategy to treat schizophrenia, epilepsy and other neuropsychiatric disorders.