Project Summary Alcohol use disorders are highly prevalent in the US and have negative personal, social, and economic consequences. The underlying circuit mechanisms, and alterations in neuronal plasticity co-opted by this disorder, however, are not well understood. Our preliminary data suggests that the neurotensin (NTS)-containing projection from the central amygdala (CeA) to the parabrachial nucleus (PBN) plays a role in modulating the rewarding properties of ethanol. Genetic ablation of NTS neurons in the CeA produces a decrease in ethanol consumption, whereas optogenetic activation of the NTSCeAPBN pathway results in reinforcing (reward-like) behaviors and enhanced ethanol drinking. Ethanol produces changes in synaptic plasticity and excitability in CeA neurons, however, the projection from the CeA to the PBN has not been investigated. The goal of this proposal is to determine the ability of excessive alcohol consumption to modulate the NTSCeAPBN pathway. The first set of experiments will use slice whole-cell electrophysiology, in a genetic- and pathway-specific manner, and in combination with optogenetics, to probe the effects of in vivo ethanol consumption on excitability and synaptic plasticity of CeA neurons that project to the PBN. The second set of experiments will use in vivo optogenetic manipulations to determine whether ethanol consumption enhances the rewarding and ethanol-seeking properties of this pathway.