Prelimbic somatostatin peptide signaling in binge ethanol consumption

Project Summary Alcohol Use Disorder (AUD) is a complex psychiatric disorder with large societal and personal strain, involving many brain regions and cell types. Few effective treatments exist that specifically target the prevention of binge drinking. Understanding the underlying neurobiology of binge drinking is essential for preventing and treating this major public health problem. Ongoing work in our lab seeks to understand how somatostatin (SST) expressing GABAergic neurons in the prelimbic (PL) cortex, which have long been implicated in other neuropsychiatric disorders as an anti-depressive, resilience-conferring population of peptidergic neurons, may function as a therapeutic target for AUD. The overarching goal of this proposal is to understand how SST peptide signaling contributes to PL circuitry function, and how these pathways are modulated by binge alcohol consumption. Using a combination of electrophysiology, circuit mapping, fiber photometry, and behavior, we will explore three complementary but non-overlapping aims: we will demonstrate how SST modulates prelimbic pyramidal neurons, the specific outputs modulated by SST, and the overall behavioral phenotype of SST administration to the PL cortex. We will conduct these experiments during control conditions and in the context of binge drinking. Taken together, these experiments will determine the overall role of SST peptide effects on pathway-specific circuits of the PL cortex. In addition, we will establish the in vivo effects of SST peptide on alcohol consumption and anxiety-like behaviors, providing an overall mechanistic and functional characterization of SST in the PL cortex. These results will build upon our previous findings to elucidate the precise role of the SST peptide. Importantly, we expect these results to have the potential to inform new treatment targets for AUD.