美国国家心理健康研究所Hugo A. Tejeda和美国匹兹堡大学Zachary Freyberg合作取得重要工作进展。他们报道了由不同腹侧纹状体多巴胺受体介导的动机和强化的可分离性调控。相关研究成果2024年12月9日在线发表于《自然—神经科学》杂志上。

据介绍，多巴胺（DA）在纹状体回路（包括伏隔核内侧壳，mNAcSh）中的释放，能够追踪奖赏的不同特征，如动机和强化。然而，多巴胺受体如何将多巴胺的释放转化为奖赏的不同构成，其细胞和回路机制仍不清楚。

研究人员表明，mNAcSh中的DA D3受体（D3R）信号通过调节局部微电路，来驱动小鼠的动机行为。

此外，D3R与DA D1受体共表达，调控强化，但不是动机。研究人员报告了mNAcSh神经元中，D3R和DA D1受体信号传导的非重叠生理作用，这与奖励功能中的可分离作用相似。

这一研究结果建立了一个基本框架，其中同一伏隔核细胞类型内的DA信号，通过对不同DA受体的作用进行生理分区。这种结构和功能组织使边缘回路中的神经元具有独特的能力，能够协调与神经精神疾病病因有关的奖赏相关行为的不同方面。

附：英文原文

Title: Dissociable control of motivation and reinforcement by distinct ventral striatal dopamine receptors

Author: Enriquez-Traba, Juan, Arenivar, Miguel, Yarur-Castillo, Hector E., Noh, Chloe, Flores, Rodolfo J., Weil, Tenley, Roy, Snehashis, Usdin, Ted B., LaGamma, Christina T., Wang, Huikun, Tsai, Valerie S., Kerspern, Damien, Moritz, Amy E., Sibley, David R., Lutas, Andrew, Moratalla, Rosario, Freyberg, Zachary, Tejeda, Hugo A.

Issue&Volume: 2024-12-09

Abstract: Dopamine (DA) release in striatal circuits, including the nucleus accumbens medial shell (mNAcSh), tracks separable features of reward like motivation and reinforcement. However, the cellular and circuit mechanisms by which DA receptors transform DA release into distinct constructs of reward remain unclear. Here we show that DA D3 receptor (D3R) signaling in the mNAcSh drives motivated behavior in mice by regulating local microcircuits. Furthermore, D3Rs coexpress with DA D1 receptors, which regulate reinforcement, but not motivation. Paralleling dissociable roles in reward function, we report nonoverlapping physiological actions of D3R and DA D1 receptor signaling in mNAcSh neurons. Our results establish a fundamental framework wherein DA signaling within the same nucleus accumbens cell type is physiologically compartmentalized via actions on distinct DA receptors. This structural and functional organization provides neurons in a limbic circuit with the unique ability to orchestrate dissociable aspects of reward-related behaviors relevant to the etiology of neuropsychiatric disorders.

DOI: 10.1038/s41593-024-01819-9

Source: https://www.nature.com/articles/s41593-024-01819-9