Alcohol Modulation of a Novel Local BNST Circuit

Univ Of North Carolina Chapel Hill, Chapel Hill NC

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): Alcohol abuse remains highly prevalent despite many decades of rigorous investigation. This is due, in part, to changes in neuronal activity following alcohol dependence that drive continued consumption of alcohol. The bed nucleus of the stria terminalis (BNST) is a central anatomical substrate that plays a role in processing cortical and limbic inputs and projects to diverse nuclei that regulate reward-related behaviors. Results from our lab and others demonstrate that chronic alcohol exposure leads to increased glutamatergic tone and excitability in the BNST. Recent work has identified a novel population of BNST vGlut3-expressing neurons, however the functional and behavioral role of these neurons remains unexplored. Behaviorally, my preliminary data show that pharmacogenetic inhibition of BNST vGlut3 neurons reduces binge ethanol consumption. Physiologically, my preliminary data highlights that BNST vGlut3 neurons provide local GABAergic inhibition and have increased excitability following withdrawal from chronic intermittent ethanol vapor exposure, a mouse model of alcohol dependence. Using slice electrophysiology in combination with optogenetics, this proposal aims to rigorously characterize how both acute alcohol exposure, and withdrawal from a chronic intermittent ethanol, impacts the membrane and local synaptic properties of BNST vGlut3 neurons. The results of this project will provide critical information about a novel circuit that may play an important role in alcohol abuse.