Optogenetic Editing Reveals the Hierarchical Organization of Learned Action Sequences.
Optogenetic Editing Reveals the Hierarchical Organization of Learned Action Sequences.
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DOI：
10.1016/j.cell.2018.06.012
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发表时间：
2018-06-28
期刊：
影响因子：
64.5
通讯作者：
Jin X
中科院分区：
文献类型：
--
作者：
Geddes CE;Li H;Jin X
将动作组织成序列是复杂行为的基础，这些行为对有机体的生存和繁殖至关重要。尽管对与中央模式生成器相关的先天序列进行了广泛的研究，但学习到的动作序列是如何控制的，以及它们是以链还是层级的形式组织起来，在很大程度上仍然是未知的。通过训练小鼠执行不同的动作序列，我们在这里证明了纹状体的直接和间接路径优先编码不同行为水平的序列结构。纹状体直接通路的状态依赖的闭环光遗传刺激可以选择性地在序列中插入单个作用元件，而不会破坏整个序列长度。纹状体间接通路的光遗传操作完全去除了正在进行的子序列，而留下了后续的子序列，以适当的时间和长度执行。这些结果表明，习得的动作序列不是以序列的形式组织起来的，而是一种明显受基底节通路控制的分层结构。对复杂行为过程中基底节回路的询问揭示了纹状体直接和间接通路明显支持的习得动作序列的层次结构。
The organization of action into sequences underlies complex behaviors that are essential for organismal survival and reproduction. Despite extensive studies of innate sequences in relation to central pattern generators, how learned action sequences are controlled, and whether they are organized as a chain or hierarchy remain largely unknown. By training mice to perform heterogeneous action sequences, here we demonstrate that striatal direct and indirect pathways preferentially encode different behavioral levels of sequence structure. State-dependent closed-loop optogenetic stimulation of the striatal direct pathway can selectively insert a single action element into the sequence without disrupting the overall sequence length. Optogenetic manipulation of the striatal indirect pathway completely removes the ongoing subsequence while leaving the following subsequence to be executed with the appropriate timing and length. These results suggest that learned action sequences are not organized in a serial but rather a hierarchical structure that is distinctly controlled by basal ganglia pathways. Interrogation of basal ganglia circuits during complex behavior unveil the hierarchical structure of learned action sequences supported distinctly by striatal direct and indirect pathways.
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