Top-down regulation of compulsive reward-seeking behavior by medial prefrontal cortex

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 DESCRIPTION (provided by applicant): While the drive to seek reward is a fundamental trait shared across many species, when left unchecked it can lead to addiction and substance abuse. A potential therapeutic approach to treating addiction could be to reset the balance between the neural circuits that drive and suppress reward-seeking. To achieve such an approach, we must characterize the specific neural state changes that occur with compulsive reward-seeking, and identify the neural pathways that can reverse this behavior. This proposal aims to use 2photon imaging to reveal the neural activity patterns in the nucleus accumbens (NAc) during a type of compulsive reward-seeking behavior, optogenetic self-stimulation of the ventral tegmental area dopamine neurons. This will reveal the changes in neural dynamics that emerge with repeated, compulsive reward-seeking which underlies addiction. In addition, this proposal will test whether medial prefrontal cortex (mPFC) stimulation is able to exert regulatory action to reduce compulsive reward-seeking by altering the neural activity patterns that are observed in NAc. Finally, this proposal aims to identify which specific mPFC projection neurons drive suppression of reward-seeking behaviors using cell type-specific rabies GCaMP6 and fiber photometry imaging. The findings from this proposed project will provide a novel insight into how NAc circuit dynamics become altered during addiction, and how these changes may be counteracted by top-down executive control from the mPFC.