Vendrell-Llopis Nuria, Read Jonathan, Boggiano Samantha, Hetzler Belinda, Peitsinis Zisis, Stanley Cherise, Visel Meike, Trauner Dirk, Donthamsetti Prashant, Carmena Jose, Lammel Stephan, Isacoff Ehud Y
Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Electrical and Computer Engineering, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Neuron. 2025 Mar 5;113(5):785-794.e9. doi: 10.1016/j.neuron.2024.12.013. Epub 2025 Jan 14.
Timed dopamine signals underlie reinforcement learning, favoring neural activity patterns that drive behaviors with positive outcomes. In the striatum, dopamine activates five dopamine receptors (D1R-D5R), which are differentially expressed in striatal neurons. However, the role of specific dopamine receptors in reinforcement is poorly understood. Using our cell-specific D1R photo-agonist, we find that D1R activation in D1-expressing neurons in the dorsomedial striatum is sufficient to reinforce preceding neural firing patterns in defined ensembles of layer 5 cortico-striatal neurons of the mouse motor cortex. The reinforcement is cumulative and time dependent, with an optimal effect when D1R activation follows the selected neural pattern after a short interval. Our results show that D1R activation in striatal neurons can selectively reinforce cortical activity patterns, independent of a behavioral outcome or a reward, crucially contributing to the fundamental mechanisms that support cognitive functions like learning, memory, and decision-making.
定时多巴胺信号是强化学习的基础，有利于驱动产生积极结果行为的神经活动模式。在纹状体中，多巴胺激活五种多巴胺受体（D1R - D5R），这些受体在纹状体神经元中差异表达。然而，特定多巴胺受体在强化过程中的作用却知之甚少。利用我们的细胞特异性D1R光激动剂，我们发现背内侧纹状体中表达D1的神经元内D1R的激活足以强化小鼠运动皮层第5层皮质 - 纹状体神经元特定组合中先前的神经放电模式。这种强化是累积性的且与时间相关，当D1R激活在短时间间隔后跟随选定的神经模式时效果最佳。我们的结果表明，纹状体神经元中D1R的激活可以选择性地强化皮层活动模式，而与行为结果或奖励无关，这对支持学习、记忆和决策等认知功能的基本机制至关重要。
