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Dryad

Cortical VIP neurons as a critical node for dopamine actions

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Nov 27, 2024 version files 3.47 GB

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Abstract

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.