Repeated binge alcohol drinking is a major public health problem and is thought to lead to pathophysiological alterations in brain circuitry that contribute to alcohol dependence and addiction. While complex behaviors such as ethanol consumption are likely controlled by a distributed, interconnected network of brain nuclei, corticotropin releasing factor (CRF) producing neurons within the central nucleus of the amygdala (CeA) are thought to play a crucial role in progressively driving pathological ethanol consumption. The CeA is composed of numerous neurochemically distinct neurons, and therefore determining how endogenous CRF signaling modulates neural circuits via their functional connectivity with postsynaptic targets has proven difficult due to technical limitations in evaluating specific long-range synaptic projections. To circumvent this, we propose to use optogenetic techniques coupled with brain slice electrophysiology and behavioral assays to examine the properties of CRF neuronal circuits in the extended amygdala and to determine whether activation or inhibition of CRF containing neural circuit elements can alter binge ethanol intake. We hypothesize that CRF producing neurons within the CeA project to the bed nucleus of the stria terminalis (BNST), and that activation of this pathway will be enhanced and required for repeated binge ethanol intake. We will test this hypothesis using a multi-disiclplinary approach combining both in vivo and ex vivo analysis of function. In total, the proposed research will provide essential information concerning the role that the CRF projection from the CeA to the BNST plays in binge ethanol drinking.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Comprehensive Center (P60)
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Special Emphasis Panel (ZAA1-GG (50))
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University of North Carolina Chapel Hill
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