Details

Autor(en) / Beteiligte

• 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

Titel

A Genetically Defined Compartmentalized Striatal Direct Pathway for Negative Reinforcement

Ist Teil von

• Cell, 2020-10, Vol.183 (1), p.211-227.e20

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• 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. [Display omitted] •Tshz1 labels a population of striatal direct pathway medium spiny neurons (dMSNs)•Tshz1-expressing (Tshz1+) dMSNs are localized in the striosome•Tshz1+ striosomal dMSNs represent punishment and drive negative reinforcement•Pdyn labels another population of striosomal dMSNs mediating positive reinforcement Xiao et al. define an unconventional component of the direct pathway for motivated behaviors crucial for aversive learning that is enriched in the striosome of the dorsal striatum and represents punishment to drive negative reinforcement in mice.