A Genetically Defined Compartmentalized Striatal Direct Pathway for Negative Reinforcement

Xiao, X., Deng, H., Furlan, A., Yang, T., Zhang, X., Hwang, G. R., Tucciarone, J., Wu, P., He, M., Palaniswamy, R., Ramakrishnan, C., Ritola, K., Hantman, A., Deisseroth, K., Osten, P., Huang, Z. J., Li, B. (October 2020) A Genetically Defined Compartmentalized Striatal Direct Pathway for Negative Reinforcement. Cell, 183 (1). 211-227.e20. ISSN 0092-8674

Abstract

The striosome compartment within the dorsal striatum has been implicated in reinforcement learning and regulation of motivation, but how striosomal neurons contribute to these functions remains elusive. Here, we show that a genetically identified striosomal population, which expresses the Teashirt family zinc finger 1 (Tshz1) and belongs to the direct pathway, drives negative reinforcement and is essential for aversive learning in mice. Contrasting a "conventional" striosomal direct pathway, the Tshz1 neurons cause aversion, movement suppression, and negative reinforcement once activated, and they receive a distinct set of synaptic inputs. These neurons are predominantly excited by punishment rather than reward and represent the anticipation of punishment or the motivation for avoidance. Furthermore, inhibiting these neurons impairs punishment-based learning without affecting reward learning or movement. These results establish a major role of striosomal neurons in behaviors reinforced by punishment and moreover uncover functions of the direct pathway unaccounted for in classic models.

Item Type:	Paper
Additional Information:	1097-4172 Xiao, Xiong Deng, Hanfei Furlan, Alessandro Yang, Tao Zhang, Xian Hwang, Ga-Ram Tucciarone, Jason Wu, Priscilla He, Miao Palaniswamy, Ramesh Ramakrishnan, Charu Ritola, Kimberly Hantman, Adam Deisseroth, Karl Osten, Pavel Huang, Z Josh Li, Bo Journal Article United States Cell. 2020 Oct 1;183(1):211-227.e20. doi: 10.1016/j.cell.2020.08.032. Epub 2020 Sep 15.
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal organism description > animal behavior organs, tissues, organelles, cell types and functions > tissues types and functions > basal ganglia bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > homeodomain protein organism description > animal behavior > learning organism description > animal > mammal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organism description > animal > mammal > rodent organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:	Li, Bo Huang, Z. Josh Osten, Pavel Xiao, Xiong Deng, Hanfei Furlan, Alessandro Yang, Tao Zhang, Xian Hwang, Ga-Ram Tucciarone, Jason Wu, Priscilla Palaniswamy, Ramesh
Communities:	CSHL labs > Huang lab CSHL labs > Li lab CSHL labs > Osten lab
Depositing User:	Matthew Dunn
Date:	1 October 2020
Date Deposited:	11 Jan 2021 21:44
Last Modified:	01 Feb 2024 19:34
PMCID:	PMC8605319
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/39888

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