加拿大麦吉尔大学Bruno Giros和比利时布鲁塞尔自由大学Alban de Kerchove d’Exaerde共同合作，近期取得重要工作进展。他们研究提出，共表达多巴胺D1和D2受体的纹状体投射神经元调节D1和D2-SPN的运动功能。相关研究成果2024年7月4日在线发表于《自然—神经科学》杂志上。

据介绍，纹状体在运动控制中的作用通常被认为是由两种纹状体传出途径介导的，这两种途径的特征是表达多巴胺（DA）D1受体或D2受体的纹状体投射神经元（SPN）（分别为D1 SPN和D2 SPN），而不考虑共表达这两种受体的SPN（D1/D2 SPN）。

研究人员开发了一种在小鼠中靶向这些杂交SPN的方法，并证明尽管这些SPN的数量较少，但它们在指导其他两个群体的运动功能方面发挥着重要作用。D1/D2 SPN专门投射到外部苍白球，具有特异的电生理特征和DA信号的独特整合。功能获得和丧失实验表明，D1/D2 SPN分别增强D1 SPN和D2 SPN的促运动和抗运动功能，并抑制对精神刺激剂的综合运动反应。

总之，这一研究结果证明了这种D1/D2共表达神经元群体在协调丘脑皮质纹状体回路中DA调节的微调中发挥了重要作用。

附：英文原文

Title: Striatal projection neurons coexpressing dopamine D1 and D2 receptors modulate the motor function of D1- and D2-SPNs

Author: Bonnavion, Patricia, Varin, Christophe, Fakhfouri, Ghazal, Martinez Olondo, Pilar, De Groote, Aurlie, Cornil, Amandine, Lorenzo Lopez, Ramiro, Pozuelo Fernandez, Elisa, Isingrini, Elsa, Rainer, Quentin, Xu, Kathleen, Tzavara, Eleni, Vigneault, Erika, Dumas, Sylvie, de Kerchove dExaerde, Alban, Giros, Bruno

Issue&Volume: 2024-07-04

Abstract: The role of the striatum in motor control is commonly assumed to be mediated by the two striatal efferent pathways characterized by striatal projection neurons (SPNs) expressing dopamine (DA) D1 receptors or D2 receptors (D1-SPNs and D2-SPNs, respectively), without regard to SPNs coexpressing both receptors (D1/D2-SPNs). Here we developed an approach to target these hybrid SPNs in mice and demonstrate that, although these SPNs are less abundant, they have a major role in guiding the motor function of the other two populations. D1/D2-SPNs project exclusively to the external globus pallidus and have specific electrophysiological features with distinctive integration of DA signals. Gain- and loss-of-function experiments indicate that D1/D2-SPNs potentiate the prokinetic and antikinetic functions of D1-SPNs and D2-SPNs, respectively, and restrain the integrated motor response to psychostimulants. Overall, our findings demonstrate the essential role of this population of D1/D2-coexpressing neurons in orchestrating the fine-tuning of DA regulation in thalamo-cortico-striatal loops.

DOI: 10.1038/s41593-024-01694-4

Source: https://www.nature.com/articles/s41593-024-01694-4