5/8 INIA Stress and Chronic Alcohol Interactions: Probing brain circuits that regulate alcohol stress interactions

Project Summary In this project we will mechanistically explore two neuromodulatory systems within the extended amydala and how they regulate plasticity and behavior following alcohol exposure and stress. In particular, in aims 1 and 2 we will utilize novel CRISPR technology to manipulate signaling in discrete brain regions, building on our prior investigations. In aim 1, we will explore the role of central amygdala (CeA) Kappa Opioid Receptor (KOR) signaling in alcohol and stress driven alterations in plasticity and in vivo dynamics of specific bed nucleus of the stria terminalis (BNST) outputs. In aim 2, we will investigate the contribution of noradrenergic signaling to alcohol drinking and alcohol driven disruptions of behavior. In aim 3, we will collaborate within and across INIA consortia in three ways (i.) investigating how CeA KOR knock out regulates alcohol exposure induced disruptions of dopamine signaling in vivo (Jones/Holleran component) , (ii.) investigating adrenergic receptor modulation in the BNST following alcohol consumption (Grant/Schnitko), (iii.) whole brain cFos analysis following GPR88 agonism to reduce alcohol consumption (Kieffer/Harsan). Thus, these integrated, yet independent aims, will provide circuit specific mechanistic findings in critical nodes that have been established to contribute to multiple aspects of the positive and negative reinforcing properties of alcohol.