Inhibitory neurons (INs) consist of distinct subtypes with unique functions. Previous studies on INs mainly focused on single brain regions, and thus it remains unclear whether the modulation of IN subtypes occurs globally across multiple regions. Here, we monitored the activity of different cortical IN subtypes at both macroscale and microscale in mice learning a lever-press task. Learning evoked a global modulation of IN subtypes throughout the cortex. The initial learning phase involved strong activation of vasoactive intestinal peptide-expressing INs (VIP-INs) and weak activation of somatostatin-expressing INs (SOM-INs). Inactivating VIP-INs increased SOM-IN activity and impaired initial learning. Concurrently, cortical cholinergic inputs from the basal forebrain were initially more active but became less engaged over learning. Manipulation of the cholinergic system impaired motor learning and differentially altered activity of IN subtypes. These results reveal that motor learning involves a global and subtype-specific modulation on cortical INs regulated by the cholinergic system.

抑制性神经元 (IN) 由具有独特功能的不同亚型组成。先前对 IN 的研究主要集中在单个大脑区域，因此尚不清楚 IN 亚型的调节是否发生在多个区域的全局范围内。在这里，我们在宏观和微观层面上监测了学习杠杆按压任务的小鼠中不同皮质 IN 亚型的活动。学习引起了整个皮层 IN 亚型的全局调节。初始学习阶段涉及表达血管活性肠肽的 IN (VIP-IN) 的强激活和表达生长抑素的 IN (SOM-IN) 的弱激活。 VIP-IN 失活会增加 SOM-IN 活性并损害初始学习。与此同时，来自基底前脑的皮质胆碱能输入最初更加活跃，但对学习的参与度降低。胆碱能系统的操纵会损害运动学习并导致 IN 亚型的活动发生差异性改变。这些结果表明，运动学习涉及受胆碱能系统调节的皮质 IN 的全局和亚型特异性调节。