Grant: Operating Grant

Learning and memory occur by changes in strengths of connections in the brain, in part by changes in the local density of neurotransmitter receptors at the postsynaptic density. We are studying two major types of neurotransmitter receptors, excitatory NMDA and inhibitory GABA receptors. Excitatory receptors increase firing rates to the next nerve cell in a circuit, whereas inhibitory receptors reduce firing rates. A balance must be maintained for brain health. Over-activation of NMDA receptors contributes to damage during stroke, and impairment of GABA receptor transmission to epilepsy. Our goal is to understand how the local density and function of these neurotransmitter receptors is determined. For example, how do individual receptor subunits and scaffolding proteins contribute to receptor trafficking? How does activity modulate this process? These studies may aid in the development of better treatments for stroke and epilepsy. Given the central role of the NMDA receptor in learning and memory, we also hope that this research will lead to the design of molecular and pharmacological therapies for improvement of learning, to maintain cognitive function in neurological disorders such as Alzheimer's disease.