Striatal dopamine contributions to skilled motor learning.
Striatal dopamine contributions to skilled motor learning.
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纹状体多巴胺对熟练运动学习的贡献。
DOI：
10.1101/2024.02.06.579240
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Burgess,ChristianR
中科院分区：
文献类型：
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作者：
Phillips,ChrisD;Myers,CourtneyC;Leventhal,DanielK;Burgess,ChristianR
协调的多关节肢体和手指运动——“手工灵巧”——是专业技能（如弹钢琴）和更平凡的任务（如系鞋带）的基础。灵巧技能的损伤会导致严重的残疾，如运动皮质损伤、帕金森氏病和一系列其他病理。临床观察和基础研究表明，皮质纹状体回路在学习和执行灵巧技能方面起着关键作用。此外，这些区域的多巴胺能信号传导与突触可塑性和运动学习有关。尽管如此，纹状体多巴胺信号在熟练运动学习中的作用仍然知之甚少。在这里，我们使用纤维光度法与基因编码的多巴胺传感器配对，研究雄性和雌性小鼠在学习和执行熟练的接触任务时纹状体多巴胺的释放。多巴胺迅速增加在熟练达到和峰值附近的颗粒消耗。在背外侧纹状体中，多巴胺动态比在背内侧和腹侧纹状体中更快。在整个训练过程中，随着成绩的提高，多巴胺信号从颗粒消耗转变为预测颗粒可用性的线索，特别是在纹状体的内侧和腹侧区域。此外，表现预测误差存在于纹状体中，在不成功到达后多巴胺释放减少。这些发现表明，熟练运动行为中的多巴胺动态随着学习而改变，并且在纹状体亚区中受到不同的调节。
Coordinated multijoint limb and digit movements—“manual dexterity”—underlie both specialized skills (e.g., playing the piano) and more mundane tasks (e.g., tying shoelaces). Impairments in dexterous skill cause significant disability, as occurs with motor cortical injury, Parkinson9s disease, and a range of other pathologies. Clinical observations, as well as basic investigations, suggest that corticostriatal circuits play a critical role in learning and performing dexterous skills. Furthermore, dopaminergic signaling in these regions is implicated in synaptic plasticity and motor learning. Nonetheless, the role of striatal dopamine signaling in skilled motor learning remains poorly understood. Here, we use fiber photometry paired with a genetically encoded dopamine sensor to investigate striatal dopamine release in both male and female mice as they learn and perform a skilled reaching task. Dopamine rapidly increases during a skilled reach and peaks near pellet consumption. In the dorsolateral striatum, dopamine dynamics are faster than in the dorsomedial and ventral striatum. Across training, as reaching performance improves, dopamine signaling shifts from pellet consumption to cues that predict pellet availability, particularly in medial and ventral areas of the striatum. Furthermore, performance prediction errors are present across the striatum, with reduced dopamine release after an unsuccessful reach. These findings show that dopamine dynamics during skilled motor behaviors change with learning and are differentially regulated across striatal subregions.