The transcription factor Npas4 regulates reward-related learning and memory

Abstract

Dopamine (DA) is necessary for motor function, motivation, working memory, and reward. However, how DA regulates reward-related learning and memorythrough the gene expression is not fully understood. Neuronal Per Arnt Sim domain protein 4 (Npas4), a brain-specific basic helix-loop-helix transcription factor, plays a role in synaptic plasticity by regulating the expression of activity-dependent genes,such as BDNF.Although Npas4 required forcontextual fear memory formation in mice, the role of Npas4 in reward-relatedlearning and memoryremains unknown. To this purpose, we used the conditioned place preference (CPP) paradigm in which animals learn to prefer a context associated with cocaine. Here, we found that the deletion of Npas4 in the accumbal D1R-expressing MSNs (D1R-MSNs) suppressedCPP. This phonotype was rescued by the D1R-MSNs specific expression of Npas4-WT but not phospho-deficient Npas4 mutant. These results suggestthat Npas4 and its phosphorylation regulate reward-related learning and memory in the accumbal D1R-MSNs.