Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Bethesda, Maryland 20892-9412, USA.
Nature. 2010 Jul 22;466(7305):457-62. doi: 10.1038/nature09263.
Learning new action sequences subserves a plethora of different abilities such as escaping a predator, playing the piano, or producing fluent speech. Proper initiation and termination of each action sequence is critical for the organization of behaviour, and is compromised in nigrostriatal disorders like Parkinson's and Huntington's diseases. Using a self-paced operant task in which mice learn to perform a particular sequence of actions to obtain an outcome, we found neural activity in nigrostriatal circuits specifically signalling the initiation or the termination of each action sequence. This start/stop activity emerged during sequence learning, was specific for particular actions, and did not reflect interval timing, movement speed or action value. Furthermore, genetically altering the function of striatal circuits disrupted the development of start/stop activity and selectively impaired sequence learning. These results have important implications for understanding the functional organization of actions and the sequence initiation and termination impairments observed in basal ganglia disorders.
学习新的动作序列有助于多种不同的能力,例如逃避捕食者、弹钢琴或流畅地说话。每个动作序列的正确启动和终止对于行为的组织至关重要,而在黑质纹状体疾病(如帕金森病和亨廷顿病)中则会受到损害。我们使用一种自我调节的操作性任务,让老鼠学习执行特定的动作序列以获得结果,发现黑质纹状体回路中的神经活动专门表示每个动作序列的启动或终止。这种开始/停止活动在序列学习期间出现,对于特定的动作具有特异性,并且不反映间隔时间、运动速度或动作值。此外,通过改变纹状体回路的功能来遗传改变会破坏开始/停止活动的发展,并选择性地损害序列学习。这些结果对于理解动作的功能组织以及在基底神经节疾病中观察到的序列启动和终止障碍具有重要意义。