Cortical VIP neurons as a critical node for dopamine actions

Although dopamine modulates diverse cognitive processes of the prefrontal
cortex including working memory, its underlying mechanisms are unclear. We
investigated the roles of prefrontal vasoactive intestinal polypeptide
(VIP)-expressing neurons, which are interneurons rich in D1 receptors
(D1Rs), in working memory in mice engaged in a delayed match-to-sample
task. VIP neurons conveyed robust working-memory signals and their
inactivation profoundly impaired behavioral performance. Also, selective
D1R knockdown in VIP neurons but not in pyramidal neurons impaired
behavioral performance, indicating that VIP neurons are the primary
mediators of dopamine effects on working memory. Additionally, we found
that delay-period dopamine release dynamics vary depending on target
location and that dopaminergic terminal stimulation increases prefrontal
neuronal target selectivity in a laterality-dependent manner. These
results indicate dopamine enhances working memory based on target
laterality. These findings shed light on dopamine-modulated prefrontal
neural processes underlying higher-order cognitive functions.