Neuroscience Graduate Program, University of Michigan, Ann Arbor, United States.
Department of Neurology, University of Michigan, Ann Arbor, United States.
Elife. 2020 Nov 27;9:e61591. doi: 10.7554/eLife.61591.
Brain dopamine is critical for normal motor control, as evidenced by its importance in Parkinson Disease and related disorders. Current hypotheses are that dopamine influences motor control by 'invigorating' movements and regulating motor learning. Most evidence for these aspects of dopamine function comes from simple tasks (e.g. lever pressing). Therefore, the influence of dopamine on motor skills requiring multi-joint coordination is unknown. To determine the effects of precisely timed dopamine manipulations on the performance of a complex, finely coordinated dexterous skill, we optogenetically stimulated or inhibited midbrain dopamine neurons as rats performed a skilled reaching task. We found that reach kinematics and coordination between gross and fine movements progressively changed with repeated manipulations. However, once established, rats transitioned abruptly between aberrant and baseline reach kinematics in a dopamine-dependent manner. These results suggest that precisely timed dopamine signals have immediate and long-term influences on motor skill performance, distinct from simply 'invigorating' movement.
大脑多巴胺对于正常的运动控制至关重要,这一点在帕金森病和相关疾病中得到了证实。目前的假设是,多巴胺通过“激发”运动和调节运动学习来影响运动控制。多巴胺功能的这些方面的大多数证据来自于简单的任务(例如按下杠杆)。因此,多巴胺对需要多关节协调的运动技能的影响是未知的。为了确定精确定时的多巴胺操作对复杂、精细协调的灵巧技能表现的影响,我们在大鼠进行熟练的抓握任务时,通过光遗传学刺激或抑制中脑多巴胺神经元。我们发现,随着重复操作,抓握运动学和粗大运动与精细运动之间的协调逐渐发生变化。然而,一旦建立起来,大鼠就会以多巴胺依赖的方式突然从异常的抓握运动学转变为基线的抓握运动学。这些结果表明,精确定时的多巴胺信号对运动技能表现有即时和长期的影响,而不仅仅是“激发”运动。