葡萄牙Champalimaud基金会Joseph J. Paton小组发现，行动抑制揭示通过纹状体回路的对立平行控制。2022年7月6日，《自然》杂志在线发表了这项成果。

据研究人员介绍，基底神经节的直接和间接途径通常被认为是分别促进和抑制行动的。然而，观察到的纹状体直接和间接中棘神经元（dMSN和iMSN）的共同激活对这一观点提出了挑战。

研究人员探索了小鼠的这些回路，它需要一系列自发的和有提示的行动，关键是需要持续的动态行动抑制期。尽管运动产生的iMSN和dMSN在感觉运动、背外侧纹状体（DLS）中共同激活，但纤维测光和光电识别的电生理记录显示，在行动抑制期间这两条通路之间存在功能对立的特征。值得注意的是，光遗传学抑制显示，DLS回路在很大程度上参与抑制而不是促进行动。具体来说，一个特定半球上的iMSN动态地参与抑制诱导对侧行动。

为了了解这种区域特定的回路功能是如何产生的，研究人员构建了一个计算强化学习模型，它再现了行为、神经活动和光遗传抑制的关键特征。该模型预测，DLS以外的平行纹状体电路学会了促进行动的功能，产生了行动的诱惑力。与此相一致的是，光遗传抑制实验显示，与DLS中的dMSN相反，关联的背内侧纹状体中的dMSN促进对侧行动。这些数据强调了多个回路和区域特定的基底神经节过程之间的相互作用是如何导致行为控制的，并确立了感觉运动间接通路在主动抑制诱惑行为中的关键作用。

附：英文原文

Title: Action suppression reveals opponent parallel control via striatal circuits

Author: Cruz, Bruno F., Guiomar, Gonalo, Soares, Sofia, Motiwala, Asma, Machens, Christian K., Paton, Joseph J.

Issue&Volume: 2022-07-06

Abstract: The direct and indirect pathways of the basal ganglia are classically thought to promote and suppress action, respectively1. However, the observed co-activation of striatal direct and indirect medium spiny neurons2 (dMSNs and iMSNs, respectively) has challenged this view. Here we study these circuits in mice performing an interval categorization task that requires a series of self-initiated and cued actions and, critically, a sustained period of dynamic action suppression. Although movement produced the co-activation of iMSNs and dMSNs in the sensorimotor, dorsolateral striatum (DLS), fibre photometry and photo-identified electrophysiological recordings revealed signatures of functional opponency between the two pathways during action suppression. Notably, optogenetic inhibition showed that DLS circuits were largely engaged to suppress—and not promote—action. Specifically, iMSNs on a given hemisphere were dynamically engaged to suppress tempting contralateral action. To understand how such regionally specific circuit function arose, we constructed a computational reinforcement learning model that reproduced key features of behaviour, neural activity and optogenetic inhibition. The model predicted that parallel striatal circuits outside the DLS learned the action-promoting functions, generating the temptation to act. Consistent with this, optogenetic inhibition experiments revealed that dMSNs in the associative, dorsomedial striatum, in contrast to those in the DLS, promote contralateral actions. These data highlight how opponent interactions between multiple circuit- and region-specific basal ganglia processes can lead to behavioural control, and establish a critical role for the sensorimotor indirect pathway in the proactive suppression of tempting actions.

DOI: 10.1038/s41586-022-04894-9

Source: https://www.nature.com/articles/s41586-022-04894-9