Sex differences in somatostatin cell dynamics and exploratory behavior after adolescent binge drinking in mice

ABSTRACT Adolescent alcohol use is a national health problem. It is associated with negative health outcomes, such as addiction and cognitive dysfunction, but relatively little is known about the mechanisms underlying sex differences in adolescent binge drinking and changes in cortical circuits involved in brain health and psychiatric conditions. In our mouse model of adolescent alcohol consumption (Drinking in the Dark, or DID), we have observed sex-dependent changes in exploratory behaviors that are associated with dysregulation of somatostatin (SST) neuronal signaling in the prelimbic cortex. Here I propose to investigate 1) the contributions of L-type calcium channels (LTCCs) as a mechanism through which SST cells are altered due to drinking and 2) the temporal relationship between altered SST cell activity and observed behavioral deficits. Male and female transgenic mice with fluorescently tagged SST cells with undergo DID prior to brain collection. Functional changes in LTCCs on SST cells will be assessed using patch-clamp electrophysiology, and LTCCs as a druggable targets will be explored with behavioral pharmacology. I will then use freely moving single-photon neuroimaging during homecage and behavioral test conditions following DID. Using this technique, we will observe the precise temporal relationship between SST cell activity and the expression of exploratory behaviors in vivo. This research will be guided by my mentorship team, which has extensive experience in electrophysiology and in vivo imaging techniques, as well as experience in postdoctoral mentorship. Thus, conducting the proposed research will simultaneously advance our understanding of the neurobiology impacted by adolescent alcohol exposure and provide me with valuable training by qualified mentors, preparing me for an academic career in alcohol research.