Alcohol action on extended amygdala glutamate synapses

摘要

Abstract Alcohol Use Disorder (AUD) is a tremendous health and financial burden on our society. A growing literature indicates that the extended amygdala plays a key role in stress-reward interactions that may mediate key behavioral responses to chronic alcohol exposure. We demonstrated that chronic intermittent alcohol exposure up regulates CRF receptor dependent augmentation of glutamate release, as well as postsynaptic NMDA receptor function at extended amygdala glutamate synapses. We propose here to test a "two-hit" model, whereby affective disruptions produced by chronic alcohol exposure and withdrawal depend upon the coordinated pre- and postsynaptic regulation of extended amygdala glutamate synapses. To enhance this trainee’s research experience and development, we propose a series of experiments to map out mechanisms by which glutamateric inputs to the BNST (from the insula) may be organized and recruited via changes in excitatory and inhibitory drive on these cells. She will explore these mechanisms in a forced abstinence model of chronic alcohol exposure, gaining ex vivo imaging and electrophysiological training, and experience with rodent alcohol exposure models. Mentorship will also focus on communication skills through manuscript preparation and preparation of posters for scientific conferences.