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皮质血管活性肠肽神经元作为多巴胺作用的关键节点。

Cortical VIP neurons as a critical node for dopamine actions.

作者信息

Bae Jung Won, Yi Jee Hyun, Choe Seo Yeon, Li Yulong, Jung Min Whan

机构信息

Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Daejeon 34141, Korea.

State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.

出版信息

Sci Adv. 2025 Jan 3;11(1):eadn3221. doi: 10.1126/sciadv.adn3221. Epub 2025 Jan 1.

DOI:10.1126/sciadv.adn3221
PMID:39742499
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11691692/
Abstract

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.

摘要

多巴胺调节前额叶皮质中的多种认知过程，但其潜在机制仍不清楚。在这里，我们使用小鼠延迟匹配样本任务研究了前额叶表达血管活性肠肽（VIP）的神经元及其D1受体（D1R）在工作记忆中的作用。VIP神经元传递强大的工作记忆信号，其失活会损害行为表现。此外，VIP神经元中D1R的选择性敲低也导致表现受损，表明VIP神经元及其D1R在支持工作记忆中起关键作用。此外，我们发现延迟期内多巴胺释放动态因目标位置而异。此外，多巴胺能终末刺激以依赖于偏侧性的方式诱导对侧反应偏差并增强神经元目标选择性。这些结果表明，前额叶多巴胺基于偏侧性调节行为反应和延迟期活动。总体而言，这些发现揭示了多巴胺调节的前额叶神经过程在高阶认知功能中的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/f37d941a654b/sciadv.adn3221-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/2a428a438b62/sciadv.adn3221-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/8b356bf788f7/sciadv.adn3221-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/3ab949abb122/sciadv.adn3221-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/fe20ec4fa656/sciadv.adn3221-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/ae978acfbf54/sciadv.adn3221-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/3050962ffa2f/sciadv.adn3221-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/9341767dd269/sciadv.adn3221-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/f37d941a654b/sciadv.adn3221-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/2a428a438b62/sciadv.adn3221-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/8b356bf788f7/sciadv.adn3221-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/3ab949abb122/sciadv.adn3221-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/fe20ec4fa656/sciadv.adn3221-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/ae978acfbf54/sciadv.adn3221-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/3050962ffa2f/sciadv.adn3221-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/9341767dd269/sciadv.adn3221-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6e4/11691692/f37d941a654b/sciadv.adn3221-f8.jpg

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