School of Optometry and Ophthalmology and Eye Hospital, The Institute of Molecular Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Department of Neurology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
Cereb Cortex. 2020 Mar 14;30(3):1366-1381. doi: 10.1093/cercor/bhz172.
The striatopallidal pathway is specialized for control of motor and motivational behaviors, but its causal role in striatal control of instrumental learning remains undefined (partly due to the confounding motor effects). Here, we leveraged the transient and "time-locked" optogenetic manipulations with the reward delivery to minimize motor confounding effect, to better define the striatopallidal control of instrumental behaviors. Optogenetic (Arch) silencing of the striatopallidal pathway in the dorsomedial striatum (DMS) and dorsolateral striatum (DLS) promoted goal-directed and habitual behaviors, respectively, without affecting acquisition of instrumental behaviors, indicating striatopallidal pathway suppression of instrumental behaviors under physiological condition. Conversely, striatopallidal pathway activation mainly affected the acquisition of instrumental behaviors with the acquisition suppression achieved by either optogenetic (ChR2) or chemicogenetic (hM3q) activation, by strong (10 mW, but not weak 1 mW) optogenetic activation, by the time-locked (but not random) optogenetic activation with the reward and by the DMS (but not DLS) striatopallidal pathway. Lastly, striatopallidal pathway modulated instrumental behaviors through striatopallidal output projections into the external globus pallidus (GPe) since optogenetic activation of the striatopallidal pathway in the DMS and of the striatopallidal output projections in the GPe similarly suppressed goal-directed behavior. Thus, the striatopallidal pathway confers distinctive and inhibitory controls of animal's sensitivity to goal-directed valuation and acquisition of instrumental behaviors under normal and over-activation conditions, through the output projections into GPe.
纹状体苍白球通路专门用于控制运动和动机行为，但它在纹状体控制工具性学习中的因果作用仍未确定（部分原因是运动混淆效应）。在这里，我们利用短暂的和“时间锁定”的光遗传学操纵与奖励传递相结合，以最小化运动混淆效应，从而更好地定义纹状体苍白球通路对工具性行为的控制。在背内侧纹状体（DMS）和背外侧纹状体（DLS）中，纹状体苍白球通路的光遗传学（Arch）沉默分别促进了目标导向和习惯性行为，而不影响工具性行为的获得，表明在生理条件下，纹状体苍白球通路抑制了工具性行为。相反，纹状体苍白球通路的激活主要影响工具性行为的获得，通过光遗传学（ChR2）或化学遗传学（hM3q）的激活，通过强（10 mW，但不是弱的 1 mW）光遗传学激活，通过与奖励相关的时间锁定（但不是随机）光遗传学激活，以及通过 DMS（而不是 DLS）纹状体苍白球通路实现获得抑制。最后，纹状体苍白球通路通过纹状体苍白球输出投射到外苍白球（GPe）来调节工具性行为，因为 DMS 中的纹状体苍白球通路和 GPe 中的纹状体苍白球输出投射的光遗传学激活同样抑制了目标导向行为。因此，纹状体苍白球通路通过投射到 GPe 的输出，在正常和过度激活条件下，为动物对目标导向估值的敏感性和工具性行为的获得提供了独特的抑制性控制。
