Glutamate is the primary excitatory neurotransmitter in the mammalian brain. Many important neural functions (including synaptic response duration, learning and memory) are thought to be dependent on specific subunit-conferred glutamate receptor properties. Changes in glutamate receptor function have also been implicated in many abnormal phenomena, such as epilepsy, schizophrenia, Alzheimer's and Huntington's diseases, neurodegenerative diseases, and excitotoxicity secondary to stroke. The broad aim of this proposal is to study how subunit composition determines glutamate receptor function and neural behavior, using the model organism C. elegans. Specifically, this proposed work will: 1) develop electrophysiological methods for reliably recording glutamate responses from identified neurons in C. elegans. 2) Characterize the glutamate response of an identified neuron in both wildtype animals and in mutants in which each glutamate receptor subunit has been deleted, and 3) Characterize behaviors mediated by the identified neuron in both wildtype and mutant animals. This project will build on the trainee's electrophysiology experience and introduce him to molecular biology and genetics while developing a powerful new model system for future work in molecular neurobiology.
