Data to Plasticity of stereotyped birdsong driven by chronic manipulation of cortical–basal ganglia activity

Cortical-basal ganglia (CBG) circuits are critical for motor learning and performance, and are a major site of pathology. In songbirds, a CBG circuit regulates moment-by-moment variability in song and also enables song plasticity. Studies have shown that variable burst firing in LMAN, the output nucleus of this CBG circuit, actively drives acute song variability, but whether and how LMAN drives long-lasting changes in song remains unclear. Here, we ask whether chronic pharmacological augmentation of LMAN bursting is sufficient to drive plasticity in birds singing stereotyped songs. We show that altered LMAN activity drives cumulative changes in acoustic structure, timing, and sequencing over multiple days, and induces repetitions and silent pauses reminiscent of human stuttering. Changes persisted when LMAN was subsequently inactivated, indicating plasticity in song motor regions. Following cessation of pharmacological treatment, acoustic features and song sequence gradually recovered to their baseline values over a period of days to weeks. Together, our findings show that augmented bursting in CBG circuitry drives plasticity in well-learned motor skills, and may inform treatments for basal ganglia movement disorders.皮层-基底神经节（Cortical-basal ganglia, CBG）环路对于运动学习与执行至关重要，同时也是病理改变的主要发生位点。在鸣禽中，此类CBG环路可调控鸣唱的实时变异，并介导鸣唱可塑性。已有研究表明，该CBG环路的输出核团LMAN中的可变爆发式放电，可主动驱动急性鸣唱变异，但LMAN是否以及如何介导鸣唱的持久性改变，目前仍不明确。本研究旨在探讨：慢性药理学增强LMAN爆发放电，是否足以让鸣唱刻板化的鸣禽产生鸣唱可塑性。研究结果显示，LMAN活动异常可在多日内逐步改变鸣唱的声学结构、时序与序列模式，并诱发类似人类口吃的重复发声与静默停顿。当后续使LMAN失活时，上述改变仍持续存在，这表明鸣唱运动脑区发生了可塑性变化。在停止药理学干预后，鸣唱的声学特征与序列模式会在数日至数周内逐步恢复至基线水平。综上，本研究结果表明，CBG环路中增强的爆发式放电可介导已熟练掌握的运动技能产生可塑性变化，该发现或可为基底神经节运动障碍的治疗提供新思路。