This is a competing renewal application for a Consortium for the Integrative Neuroscience Initiative on Alcoholism (INIA)-West (Notice* NOT-AA-06-101) to identify the molecular, cellular, and behavioral neuroadaptations that occur in specific brain neurocircuitries that result in excessive alcohol consumption. More specifically, the focus of this multidisciplinary initiative will be on the molecular and cellular neuroadaptations in the brain reward circuits associated with the extended amygdala and its connections. The overall hypothesis for INIA-West is that genetic differences and/or neuroadaptations in this circuitry are responsible for the individual differences in vulnerability to the excessive consumption of alcohol. The overall goals of INIA-West are to identify the neurocircuitry and neurobiology responsible for excessive alcohol intake, and to provide the foundation to enable translation of the basic neuroscience findings to the human clinical condition. To accomplish these goals, the following Specific Aims are outlined: (1) To identify specific clusters of genes whose expression is regulated by alcohol and which are responsible for INIA-developed models of excessive alcohol consumption, (2) To confirm gene targets nominated by expression assays or other methods, by use of transgenic, knockout, inducible knockouts, site-specific knockouts, RNAi, and in situ hybridization, (3) To attract new and innovative investigators to the field of alcohol research. The structure of INIA-West is envisioned as two domains (Binge and Dependence) that integrate across three levels of analysis: molecular, cellular, neurocircuitry. Distributed Core facilities are proposed that transcend domains and include the Gene Array Cores, Animal Models Cores (rat and mouse) and the Neurocircuitry Cores. Each Domain is comprised of 10-12 U01 proposals and 1-2 Developmental U01 proposals. A Pilot Project program is proposed to identify exciting new areas of research and the continual recruitment of new investigators to the alcohol field. The INIA program will be directed by an Administrative Core in close cooperation with the Executive Committee, Steering Committee, and with the continual advice of the Scientific Advisory Board. ? ? ?
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