Psychology Department, Utrecht University, Yalelaan 2, 3584 CM Utrecht, the Netherlands; Biology Department, Tufts University, 200 Boston Avenue, Medford, MA 02155, USA.
Biology Department, Tufts University, 200 Boston Avenue, Medford, MA 02155, USA.
Curr Biol. 2021 Jun 21;31(12):2619-2632.e4. doi: 10.1016/j.cub.2021.04.030. Epub 2021 May 10.
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.
皮质基底神经节 (CBG) 回路对于运动学习和表现至关重要，也是病变的主要部位。在鸣禽中，CBG 回路调节着歌曲中瞬息万变的旋律，同时也使歌曲具有可塑性。研究表明，在这个 CBG 回路的输出核 LMAN 中，爆发性的放电活动积极驱动了急性歌曲的多变性，但 LMAN 是否以及如何驱动歌曲的持久变化尚不清楚。在这里，我们想知道慢性药理学增强 LMAN 爆发是否足以驱动刻板歌唱鸟类的可塑性。我们发现，改变 LMAN 的活动会导致在多个日期间声学结构、时间和序列的累积变化，并诱导出类似于人类口吃的重复和无声停顿。当 LMAN 随后被失活时，这些变化仍然存在，表明歌曲运动区域的可塑性。在停止药物治疗后，声学特征和歌曲序列在几天到几周的时间内逐渐恢复到基线值。总之，我们的发现表明，CBG 回路中增强的爆发驱动了已熟练掌握的运动技能的可塑性，这可能为基底神经节运动障碍的治疗提供信息。
