Division of Brain Sciences, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
Division of Social Pharmacy, Center for Social Pharmacy and Pharmaceutical Care Sciences, Keio University Faculty of Pharmacy, Tokyo, Japan.
Neuropsychopharmacol Rep. 2023 Sep;43(3):414-424. doi: 10.1002/npr2.12369. Epub 2023 Aug 8.
Contrary to the previous notion that the dorsomedial striatum (DMS) is crucial for acquiring new learning, accumulated evidence has suggested that the DMS also plays a role in the execution of already learned action sequences. Here, we examined how the direct and indirect pathways in the DMS regulate action sequences using a task that requires animals to press a lever consecutively. Cell-type-specific bulk Ca recording revealed that the direct pathway was inhibited at the time of sequence execution. The sequence-related response was blunted in trials where the sequential behaviors were disrupted. Optogenetic activation at the sequence start caused distraction of action sequences without affecting motor function or memory of the task structure. By contrast with the direct pathway, the indirect pathway was slightly activated at the start of the sequence, but the optogenetic suppression of such sequence-related signaling did not impact the behaviors. These results suggest that the inhibition of the DMS direct pathway promotes sequence execution potentially by suppressing the formation of a new association.
与先前认为背内侧纹状体（DMS）对于获取新学习至关重要的观点相反，越来越多的证据表明，DMS 也在已经学习的动作序列的执行中发挥作用。在这里，我们使用需要动物连续按下杠杆的任务来检查 DMS 中的直接和间接通路如何调节动作序列。细胞类型特异性批量 Ca 记录显示，在序列执行时直接通路被抑制。在行为序列中断的试验中，与序列相关的反应减弱。在序列开始时进行光遗传学激活会导致动作序列分心，而不会影响运动功能或任务结构的记忆。与直接通路相反，间接通路在序列开始时略有激活，但对这种与序列相关的信号的光遗传学抑制不会影响行为。这些结果表明，DMS 直接通路的抑制通过抑制新关联的形成来促进序列执行。
