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The Wills lab is focused on understanding the neuroadaptations that occur in alcohol dependence, particularly those produced by adolescent alcohol use. To do this, we utilize a wide range of techniques that include electrophysiology, proteomics, and behavioral analysis using a rodent model of alcohol dependence. Much of our work evaluates alcohol-induced changes in the bed nucleus of the stria terminalis (BNST), a region critical for relapse. Further, our studies in this region have highlighted a key role of NMDA receptor signaling in alcohol’s effects.

Below are brief summaries of our current projects:

1.  Adolescent Alcohol Use

This research will evaluate the dynamic regulation of NMDAR subunit composition and signaling during adolescence, which is a population vulnerable to alcohol addiction. In adults, GluN2B-NMDAR signaling is highly regulated by alcohol in the BNST. Previous work in the BNST demonstrated that NMDAR transmission is uniquely altered by alcohol. Future studies will utilize a combination of electrophysiology and proteomics to explore alcohol-induced changes in NMDAR function and signaling following adolescent alcohol exposure.




2.  NMDA Receptor Trafficking

This work will examine the mechanisms by which withdrawal from chronic alcohol exposure relocalizes NMDA receptors from synaptic to extrasynaptic domains. Our pervious work finds that GluN2B-NMDA receptors dissociate from PSD scaffolding proteins during alcohol withdrawal. Future work will further evaluate these mechanisms and determine how NMDA receptor relocation may alter signaling.