Basal Forebrain Cholinergic Neurons Selectively Drive Coordinated Motor Learning in Mice
Basal Forebrain Cholinergic Neurons Selectively Drive Coordinated Motor Learning in Mice
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DOI：
10.1523/jneurosci.1152-21.2021
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发表时间：
2021-12-08
影响因子：
5.3
通讯作者：
Hollis, Edmund
中科院分区：
文献类型：
--
作者：
Li, Yue;Hollis, Edmund
运动控制需要在不同的运动中心进行精确的时间和空间编码，并通过重复学习来完善。运动区域的招募需要调节性输入来塑造电路活动。在这里，我们确定了基底-皮质胆碱能通路在小鼠协调运动技能习得中的作用。基底前脑胆碱能神经元的定向耗竭导致协调运动的旋转任务训练的显著损伤。训练过程中需要胆碱能神经调节，因为胆碱能神经元的化学发生失活也会损害任务习得。已知旋转杆学习可以驱动内侧前额叶皮层（mPFC）和运动皮层中皮质纹状体神经元的细化，并且我们已经发现，任务习得需要向两个运动区域输入胆碱能。关键的是，胆碱能神经调节的作用仅限于习得阶段，因为学习后基底前脑胆碱能神经元的消耗并不影响任务执行。我们的研究结果表明，在协调运动学习过程中，远端皮层运动中心的胆碱能神经调节起着至关重要的作用。
Motor control requires precise temporal and spatial encoding across distinct motor centers that is refined through the repetition of learning. The recruitment of motor regions requires modulatory input to shape circuit activity. Here, we identify a role for the baso-cortical cholinergic pathway in the acquisition of a coordinated motor skill in mice. Targeted depletion of basal forebrain cholinergic neurons results in significant impairments in training on the rotarod task of coordinated movement. Cholinergic neuromodulation is required during training sessions as chemogenetic inactivation of cholinergic neurons also impairs task acquisition. Rotarod learning is known to drive refinement of corticostriatal neurons arising in both medial prefrontal cortex (mPFC) and motor cortex, and we have found that cholinergic input to both motor regions is required for task acquisition. Critically, the effects of cholinergic neuromodulation are restricted to the acquisition stage, as depletion of basal forebrain cholinergic neurons after learning does not affect task execution. Our results indicate a critical role for cholinergic neuromodulation of distant cortical motor centers during coordinated motor learning.