{Reference Type}: Journal Article
{Title}: NPAS4 supports cocaine-conditioned cues in rodents by controlling the cell type-specific activation balance in the nucleus accumbens.
{Author}: Hughes BW;Huebschman JL;Tsvetkov E;Siemsen BM;Snyder KK;Akiki RM;Wood DJ;Penrod RD;Scofield MD;Berto S;Taniguchi M;Cowan CW;
{Journal}: Nat Commun
{Volume}: 15
{Issue}: 1
{Year}: 2024 Aug 8
{Factor}: 17.694
{DOI}: 10.1038/s41467-024-50099-1
{Abstract}: Powerful associations that link drugs of abuse with cues in the drug-paired environment often serve as prepotent relapse triggers. Drug-associated contexts and cues activate ensembles of nucleus accumbens (NAc) neurons, including D1-class medium spiny neurons (MSNs) that typically promote, and D2-class MSNs that typically oppose, drug seeking. We found that in mice, cocaine conditioning upregulated transiently the activity-regulated transcription factor, Neuronal PAS Domain Protein 4 (NPAS4), in a small subset of NAc neurons. The NPAS4+ NAc ensemble was required for cocaine conditioned place preference. We also observed that NPAS4 functions within NAc D2-, but not D1-, MSNs to support cocaine-context associations and cue-induced cocaine, but not sucrose, seeking. Together, our data show that the NPAS4+ ensemble of NAc neurons is essential for cocaine-context associations in mice, and that NPAS4 itself functions in NAc D2-MSNs to support cocaine-context associations by suppressing drug-induced counteradaptations that oppose relapse-related behaviour.