National Institute on Drug Abuse 5R01DA062024-02

Molecular determinants of ensemble recruitment by drugs of abuse

NIH funded research project at Vanderbilt University studying molecular and epigenetic mechanisms in cocaine use disorder, focusing on neuronal ensemble dynamics in the brain's nucleus accumbens.

Description

This project focuses on how cocaine-activated ensembles are recruited initially and how these ensembles undergo changes over time to drive behaviors associated with cocaine use disorder. Epigenetic mechanisms, which trigger long-lasting changes in transcription, are identified as mediators of drug-induced adaptation within the brain. The study will investigate the role of lysine acetyltransferase 2a (KAT2a/Gcn5) in regulating cocaine reinforcement, plasticity, and ensemble expression in the nucleus accumbens (NAc). Using single nucleus RNA sequencing (snRNAseq), ensemble-specific epigenetic profiling, and cellular resolution imaging in awake and behaving animals, the project aims to track the same cells over time to understand how KAT2a influences ensemble selection and maintenance, and whether it is the initial cocaine ensemble that undergoes plasticity following cocaine self-administration or if a new ensemble is recruited by repeated drug exposure.

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