Research Component 1: Woodward

Effect of Chronic Alcohol Exposure on OFC-BLA-Striatal Circuitry and Excessive Alcohol Drinking

Principal Investigator: John J. Woodward, Ph.D.

This research project focuses on the role of chronic alcohol-induced adaptations in orbitofrontal cortex (OFC) in mediating dependence-related excessive alcohol drinking. The project extends analysis to adaptations in cortico-limbic-striatal circuitry that may underlie heavy, compulsive-like alcohol drinking associated with dependence. Specifically, studies will use chronic alcohol (CIE)-treated mice generated by the ARC Animal Core along with electrophysiology, optogenetic, and fiber photometry (calcium imaging) approaches to test the overarching hypothesis that chronic alcohol produces adaptations in convergent glutamatergic inputs to the dorsal striatum arising from the lateral OFC and basolateral amygdala (BLA), and whether these adaptations contribute to excessive, compulsive-like alcohol drinking associated with dependence.

Specific Aims of the project include:

• Test the hypothesis that the excitability and alcohol sensitivity of OFC and BLA neurons projecting to the dorsal striatum are altered by repeated cycles of CIE exposure.
• Test the hypothesis that the in vivo activity of OFC and BLA neurons projecting to the dorsal striatum during alcohol drinking is altered by repeated cycles of CIE exposure.
• Test the hypothesis that real-time manipulation of OFC and BLA neurons projecting to dorsal striatum alters drinking in Air (control) and CIE-exposed mice.