Cell
Volume 174, Issue 1, 28 June 2018, Pages 32-43.e15
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Article
Optogenetic Editing Reveals the Hierarchical Organization of Learned Action Sequences

https://doi.org/10.1016/j.cell.2018.06.012Get rights and content
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Highlights

  • Non-back-propagation learning of sequences depends on striatal NMDA receptors

  • Striatal direct pathway facilitates actions and controls sequence start/stop

  • Striatal indirect pathway inhibits actions and mediates subsequence switch

  • Optogenetic manipulations unveil the hierarchical structure of learned sequences

Summary

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 a hierarchy remain largely unknown. By training mice to perform heterogeneous action sequences, 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.

Keywords

action sequence
basal ganglia
direct pathway
indirect pathway
electrophysiology
optogenetics
striatum

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