CTNA Overall John Krystal, M.D. Abstract The gap between basic research advances and new clinical insights and treatments remains a critical obstacle to progress in the field of alcoholism research. This translational neuroscience mission is the enduring focus of the Center for the Translational Neuroscience of Alcoholism (CTNA). CTNA conducts groundbreaking molecular neuroscience, molecular genetics, functional and chemical neuroimaging, and psychopharmacology studies in the service of providing new insights to bridge the gap between basic and clinical research. This renewal application will study how inhibition of mGluR5 might normalize disturbances in cortico-striatal glutamate signaling arising from upregulation of NMDA-R and, in so doing, attenuate both goal- oriented (model-based learning) and habitual (model-free learning) alcohol consumption in animals and reduce alcohol consumption in human heavy drinkers. In so doing, we propose the first translational neuroscience evaluation of the therapeutic potential of mGluR5 NAM’s, a mechanism that has received intensive preclinical study. Building upon its prior achievements, The CTNA will facilitate transdisciplinary research within projects and across projects and with other alcohol focused initiatives nationally. It will also continue its highly productive Pilot Projects Core that provides an open competitive mechanism to enable the Center to rapidly encompass innovative new research and to engage outstanding investigators new to alcoholism research. CTNA will continue to expand its educational mission, building on the success of the the International Conference on the Applications of Neuroimaging to Alcoholism.