Examining somatostatin receptor pathways following binge drinking: a focus on PFC-->PAG projections

The National Institute on Alcohol Abuse and Alcoholism awarded The Pennsylvania State University $153,560 on December 10, 2026, under the Alcohol Research Programs (CFDA 93.273) to conduct research examining somatostatin receptor pathways following binge drinking with a focus on prefrontal cortex to periaqueductal gray (PFC→PAG) projections.

The research uses the Drinking in the Dark model of voluntary binge-like alcohol consumption in mice to investigate how alcohol-induced reductions in somatostatin expression within the prefrontal cortex affect downstream brain regions and networks. Aim 1 applies patch-clamp electrophysiology to assess alcohol-induced changes in somatostatin effects on PFC-PAG projections and evaluate functional impacts on specific neurons. Aim 2 employs in vivo neuroimaging in both head-fixed and freely moving mice to investigate how binge drinking alters somatostatin-driven changes in PFC-PAG glutamate projections and assess changes in somatostatin and PAG-projecting neuron activity. The fellowship supports the recipient's career development toward independent faculty status and provides training in alcohol models, electrophysiology, in vivo imaging, and computational analysis.

Performance occurs in State College, Pennsylvania, with a period of performance through June 30, 2029. This is a Project Grant assistance type.

Abstract

Alcohol use disorder (AUD) is a common condition affecting over 10% of people aged 12 and older, with binge drinking (4-5 drinks within 2 hours) among the riskiest forms seen in 1 in 6 adults. Despite this, the biological underpinnings of AUD are not fully understood, and there remains a critical need for improved treatments. Somatostatin (SST), a neuropeptide implicated in psychiatric disorders, has shown links to AUD in both preclinical models and humans. Studies indicate that alcohol intake reduces SST expression, particularly within the prefrontal cortex (PFC), where SST influences neuronal signaling. However, little is known about how this alcohol-induced reduction PFC SST function affects downstream brain regions and networks. This fellowship aims to investigate the role of SST signaling onto PFC outputs to the periaqueductal gray (PAG), a pathway involved in pain and behavior modulation, which are altered in AUD. Using the 'drinking in the dark' (did) model of voluntary binge-like alcohol consumption in mice, this study will examine alcohol-induced changes in SST function. Aim 1 will assess did-induced changes in SST effect onto PFC→PAG projections using patch-clamp electrophysiology to evaluate functional impacts on specific neurons. Aim 2 will investigate how binge drinking alters SST-driven changes in PFC→PAG glutamate projections using in vivo neuroimaging to assess changes in SST and PAG-projecting neuron activity in both headfixed and freely moving mice. This fellowship will support my career goal of becoming an independent faculty scientist, with a research program exploring how chronic pain-induced changes in physiologcy impact drug effects at molecular, neuronal, and behavioral levels. I will receive expert training in alcohol models, electrophysiology, in vivo imaging, and computational analysis. This F32 fellowship will support my scientific growth in key areas with guidance from expert mentors DRS. Crowley and drew and has clear future directions for a subsequent K99/R00 application.