Research Component 3: Chandler & Griffin

Adaptations in Corticostriatal Networks in Alcohol Dependence Related Goal-Directed and Habitual Drinking

Principal Investigator: L. Judson Chandler, Ph.D.
Co-Investigator: William C. Griffin, Ph.D.

The overarching hypothesis being tested in this project is that chronic alcohol exposure facilitates the expression of habitual responding for alcohol, and adaptations in specific subpopulations of neurons within the medial prefrontal cortex (mPFC) play a critical role in this process. Specifically, studies will examine chronic alcohol-induced adaptations in dopamine (DA) D1-like and D2-like expressing neurons in a sub-region of the mPFC - the infralimbic (IfL) cortex (ventromedial PFC) as part of corticostriatal networks that contribute to the shift in bias from goal-directed to habit-based motivated behavior (inflexible, excessive alcohol self-administration associated with dependence). Studies will use chronic alcohol (CIE)-treated mice generated by the ARC Animal Core and employ in vivo multielectrode recordings, fiber photometry of calcium transients, targeted (cell-specific) chemogenetic manipulations, and patch-clamp electrophysiology to address the overall study hypotheses in a comprehensive manner.

Specific Aims of the project include:

• Test the hypothesis that dependence-induced facilitation of habitual responding for alcohol is associated with changes in population activity and network organization in the intralimbic (IfL) cortex.
• Test the hypothesis that DA D1 and D2 receptor-expressing neurons in the IfL cortex modulate dependence-induced facilitation of the expression of habitual responding for alcohol.
• Test the hypothesis that dependence-induced facilitation of habitual responding for alcohol is associated with alterations in the biophysical properties of DA D1 and D2 receptor-expressing neurons in the IfL cortex.