Nature Neuroscience ( IF 21.2 ) Pub Date : 2024-12-09 , DOI: 10.1038/s41593-024-01819-9 Juan Enriquez-Traba, Miguel Arenivar, Hector E. Yarur-Castillo, Chloe Noh, Rodolfo J. Flores, Tenley Weil, Snehashis Roy, Ted B. Usdin, Christina T. LaGamma, Huikun Wang, Valerie S. Tsai, Damien Kerspern, Amy E. Moritz, David R. Sibley, Andrew Lutas, Rosario Moratalla, Zachary Freyberg, Hugo A. Tejeda
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.
中文翻译:
不同的腹侧纹状体多巴胺受体对动机和强化的解离控制
纹状体回路中的多巴胺 (DA) 释放,包括伏隔核内侧壳 (mNAcSh),跟踪奖励的可分离特征,如激励和强化。然而,DA 受体将 DA 释放转化为不同奖励结构的细胞和回路机制仍不清楚。在这里,我们表明 mNAcSh 中的 DA D3 受体 (D3R) 信号转导通过调节局部微电路来驱动小鼠的动机行为。此外,D3Rs 与 DA D1 受体共表达,DA D1 受体调节强化,但不调节动机。与奖励功能中的解离作用平行,我们报道了 mNAcSh 神经元中 D3R 和 DA D1 受体信号传导的非重叠生理作用。我们的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 信号传导通过对不同 DA 受体的作用在生理上被分隔。这种结构和功能组织为边缘回路中的神经元提供了独特的能力,可以协调与神经精神疾病病因相关的奖励相关行为的可分离方面。