Concurrent activation of striatal direct and indirect pathways during action initiation.
Concurrent activation of striatal direct and indirect pathways during action initiation.
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DOI：
10.1038/nature11846
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发表时间：
2013-02-14
期刊：
影响因子：
64.8
通讯作者：
Costa, Rui M.
中科院分区：
文献类型：
--
作者：
Cui, Guohong;Jun, Sang Beom;Jin, Xin;Pham, Michael D.;Vogel, Steven S.;Lovinger, David M.;Costa, Rui M.
基底神经节是控制自主动作的皮质下核团，并且受到许多使人衰弱的神经系统疾病的影响。基底神经节功能的流行模型提出，源自纹状体中不同群体的多刺投射神经元（spiny projection neurons，SPN）的两个正交投射回路--所谓的直接和间接通路--对运动具有相反的影响：据称直接通路SPN的活动促进运动，而间接通路SPN的活动抑制运动。由于缺乏选择性测量自由活动动物中直接和间接途径SPN活性的方法，该模型一直难以测试。我们开发了一种新的体内方法，使我们能够使用D1-Cre（直接途径特异性）和A2 A-Cre（间接途径特异性）小鼠背侧纹状体中遗传编码钙指示剂（GECI）GCAMP 3的Cre依赖性病毒表达来特异性测量直接和间接途径SPN活性。使用光纤和时间相关的单光子计数（TCSPC）在小鼠执行操作性任务，我们观察到短暂的增加，在直接和间接途径的SPNs的神经活动时，动物发起的行动，但不是当他们不活跃。同时激活的SPN从两个途径在一个半球之前开始的contraversive运动，并预测发生特定的运动在500毫秒内。这些观察结果挑战了经典的观点基底神经节功能，并可能有影响了解运动症状的起源在基底神经节疾病。
The basal ganglia are subcortical nuclei that control voluntary actions, and are affected by a number of debilitating neurological disorders. The prevailing model of basal ganglia function proposes that two orthogonal projection circuits originating from distinct populations of spiny projection neurons (SPNs) in the striatum - the so-called direct and indirect pathways - have opposing effects on movement: while activity of direct-pathway SPNs purportedly facilitates movement, activity of indirect-pathway SPNs inhibits movement. This model has been difficult to test due to the lack of methods to selectively measure the activity of direct- and indirect-pathway SPNs in freely moving animals. We developed a novel in-vivo method that allowed us to specifically measure direct- and indirect-pathway SPN activity using Cre-dependent viral expression of the genetically encoded calcium indicator (GECI) GCAMP3 in the dorsal striatum of D1-Cre (direct-pathway specific) and A2A-Cre (indirect-pathway specific) mice. Using fiber optics and time-correlated single photon counting (TCSPC) in mice performing an operant task, we observed transient increases in neural activity in both direct- and indirect-pathway SPNs when animals initiated actions, but not when they were inactive. Concurrent activation of SPNs from both pathways in one hemisphere preceded the initiation of contraversive movements, and predicted the occurrence of specific movements within 500 ms. These observations challenge the classical view of basal ganglia function, and may have implications for understanding the origin of motor symptoms in basal ganglia disorders.
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影响因子：
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