PROJECT SUMMARY/ABSTRACT Although most adults in the United States will drink alcohol in their life, only about 6% will go on to develop an alcohol use disorder (AUD). We understand the cycle of addiction, but it remains unclear why certain people transition to disordered drinking. Disturbed network activity in regions implicated in AUDs, like the basolateral amygdala (BLA), has been suggested as a potential explanation. Our preliminary data demonstrates that alcohol can modulate BLA network activity and the intrinsic differences in BLA activity in response to acute alcohol exposure can predict future alcohol consumption in an intermittent access (IA) paradigm. This current proposal aims to understand the cellular mechanism underlying this relationship. Our lab has shown that GABAergic parvalbumin (PV) interneurons are crucial modulators of network activity in the BLA. Therefore, mechanisms that control PV interneurons are positioned to influence communication in the region. Further, our lab has demonstrated that δ subunit containing GABAA receptors, which are uniquely sensitive to the effects of alcohol, are highly expressed on PV interneurons in the BLA. These receptors also influence alcohol intake in a voluntary binge drinking paradigm and anxiety-like behavior in withdrawal. Therefore, we hypothesize that alcohol modulates network activity in the BLA through δ-GABAA receptors on PV interneurons in the BLA which influences levels of future voluntary alcohol intake. We will build on our preliminary data showing that BLA responses to acute alcohol can predict alcohol consumption in an IA paradigm by investigating the mechanisms contributing to excessive alcohol intake. The current project will determine if the GABAAR δ subunit mediates alcohol’s effects on BLA oscillations by a CRISPR mediated deletion of the GABAAR δ subunit gene (Gabrd) specifically on PV interneurons in the BLA and recording local field potentials (LFPs) in the BLA during acute exposure to alcohol and an IA paradigm. The experiments in this proposed project will provide novel insight into how alcohol changes the network activity of the BLA. Further, the observed relationship between the BLA response to acute alcohol and future alcohol consumption may serve as a potential biomarker for alcohol misuse. The mentorship from my sponsor, Dr. Maguire, and my co-sponsor, Dr. Miczek, will provide me with exceptional support and resources to complete the proposed experiments. Further, the rigorous environment at Tufts will continue to challenge and support my academic growth.