RESEARCH SUMMARY Alcohol use disorder (AUD) accounts for the largest percentage of active substance use disorders. One prominent trait of AUD is compulsive use despite adverse consequences. Previous work has found that animals who drink alcohol in excess display diminished lateral habenula (LHb) activity, a brain region widely acknowledged to participate in aversive behaviors, suggesting that LHb hypoactivity may be an integral factor in compulsive alcohol use. However, mechanisms that contribute to these reductions in LHb activity have not been fully explored. Comprehensive assessment of LHb plasticity in preclinical models of AUD through the measurement of afferent neurotransmission dynamics could offer potential insight into a neurobiological basis for the reduced LHb activity observed in aversion resistance. One afferent region of particular interest is the ventral pallidum (VP). Recent findings have shown that VP glutamate (VPGlu) neurons, which project extensively into the LHb, contribute to adaptive constraint of natural reward consumption and reduction of drug-seeking actions. Yet, there remains a significant knowledge gap concerning potential alterations of LHb-projecting VP neurons that arise in response to the development of aversion-resistant alcohol use. Clarifying the changes that occur in both multiregional and VP-specific afferent input is necessary to improve our understanding of physiological alterations preventing normative aversive behavior in aversion-resistant drinking. Thus, the broad goal of the proposed work is to elucidate neurobiological adaptations of LHb afferent projections during compulsive alcohol consumption. The primary objective of this proposal is twofold: first, to investigate the impact of alcohol use on afferent neurotransmission into the LHb during aversion resistant alcohol consumption, and second, to explore the significance of VP-to-LHb projections in this behavior. Given that afferent input from several distinct brain regions has been shown to influence aversive behavior and alcohol misuse, I hypothesize that LHb afferent neurotransmission is adaptably dysregulated in animals that exhibit aversion resistant alcohol use, which may be due in part to changes in activity of VP inputs. To test this hypothesis, I will use in vivo fiber photometry to record neurotransmitter activity in the LHb and optogenetics to manipulate VP-to-LHb projections during aversion-resistant alcohol consumption alongside histological techniques to quantify neurochemical content of LHb projections. Experiments proposed here will advance our understanding of the neural mechanisms underlying aversion-resistant alcohol use, establishing a foundation for future research examining LHb-associated neural circuitry in compulsive alcohol use. Throughout this proposal, I will gain valuable training in the execution of behavioral neuroscience experiments, in vivo neurotransmitter recording methods, neuronal manipulation techniques, histologic...