The Role of the BNST to VTA Neural Circuit in Binge Alcohol Consumption

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Project Summary/Abstract Binge alcohol consumption is one of the more problematic components of alcoholism and is the third leading cause of preventable death in the USA (Hingson et al., 2005; 2007; Moklad et al., 2001). Defining the neural circuitry that modulates excessive binge alcohol intake is essential for developing effective therapeutics to treat this disease. The bed nucleus of the stria terminalis (BNST) to the ventral tegmental area (VTA) neural pathway remains a particularly interesting candidate in regards to binge alcohol consumption, as this circuit has been implicated in playing a key role in drug and alcohol addiction. I hypothesize that repeated binge alcohol exposure leads to a depotentiation of VTA-projecting BNST GABAergic neurons as well as a progressive enhancement of VTA-projecting BNST glutamatergic neurons, which facilitates further binge drinking. The goals of this proposal are to provide a thorough examination of the BNST-VTA neural circuit after repeated binge ethanol consumption as well as to transition to an independent research career at an alcohol research center during the R00 component. To complete the first goal, I will learn in vivo electrophysiology to examine alterations in BNST neurons after repeated binge ethanol drinking. During the R00 phase, I will utilize patch clamp electrophysiology to examine the excitability of VTA-projecting BNST GABAergic and glutamatergic neurons to determine the cellular mechanisms that are altered after repeated binge alcohol drinking. Finally, I will use optogenetics in freely behaving mice to stimulate the BNST GABAergic projection neurons in the VTA in order to reduce alcohol consumption as well as stimulate the BNST glutamatergic projection neurons in the VTA to increase binge ethanol intake. Taken together, this proposal will provide a thorough characterization of the BNST-VTA neural circuit after repeated binge alcohol intake and may identify possible pharmacological targets for the treatment of alcoholism.