Cortical VIP neurons as a critical node for dopamine actions | Science Advances

Dopamine modulates a wide range of cognitive processes in the prefrontal cortex, but the underlying mechanisms remain unclear. Here, we examined the roles of prefrontal vasoactive intestinal polypeptide (VIP)–expressing neurons and their D1 receptors (D1Rs) in working memory using a delayed match-to-sample task in mice. VIP neurons conveyed robust working-memory signals, and their inactivation impaired behavioral performance. Moreover, selective knockdown of D1Rs in VIP neurons also resulted in impaired performance, indicating the critical role of VIP neurons and their D1Rs in supporting working memory. Additionally, we found that dopamine release dynamics during the delay period varied depending on the target location. Furthermore, dopaminergic terminal stimulation induced a contralateral response bias and enhanced neuronal target selectivity in a laterality-dependent manner. These results suggest that prefrontal dopamine modulates behavioral responses and delay-period activity based on laterality. Overall, these findings shed light on dopamine-modulated prefrontal neural processes underlying higher-order cognitive functions.