Effects of chemogenetic modulation of MSglu on NAc DA responses during strategy switching

Authors

• A Hara
• J DiSapio
• M Coombs
• G Khayrullina
• V Joshi
• M Watowich
• M Watanabe
• K Smith
• J Gumperz
• M Gilbert
• A Howell
• M Terabe

Abstract

Maladaptation in reward-seeking is an important aspect in the development and maintenance of substance use disorders (SUDs) and understanding brain mechanisms involved in reward-seeking is a crucial first step towards developing therapeutics for SUD. Emerging evidence suggest a brain region called the medial septum (MS) is involved in reward-seeking behaviors. The MS has been found to generate reward signals when electrically stimulated, and it was recently shown that mice lever-press to earn optogenetic stimulation of specifically MS glutamate neurons (MSGLUn). Excitation of MSGLUn can influence canonical reward circuitry leading to dopamine (DA) release in the nucleus accumbens (NAcDA), a primary component of reward-seeking. Our lab found chemogenetic modulation of MSGLUn had little effect on reward-seeking behavior, but these modulations evoked changes in reward seeking strategy. Here we sought to elucidate the regulatory role of MSGLUn on NAcDA that mediate strategy switching. We found that chemogenetic excitation of MSGLUn during strategy switching correlated with increased NAcDA in response to unexpected rewards compared to NAcDA responses expressed in inactivation and control groups. Once cues were learned, chemogenetic excitation of MSGLUn showed higher NAcDA in response to the learned signal than controls, suggesting MSGLUn is involved in NAcDA release during strategy switching tasks. In future studies, we aim to continue using fiber photometry to better understand interactions between MSGLUn and NAcDA amid reward-seeking and strategy switching. Findings may enhance our understanding of how this circuitry may contribute to substance use disorders and guide the development of new therapeutic techniques.

Scientific Focus Area: ACI/IRS

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