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.

纹状体背侧的纹状体隔室与强化学习和动机调节有关，但纹状体神经元如何促进这些功能仍然难以捉摸。在这里，我们展示了基因鉴定的纹状体种群，它表达Teashirt 家族锌指 1 ( Tshz1 ) 并属于直接途径，驱动负强化，并且对于小鼠的厌恶学习至关重要。对比“传统”纹状体直接通路，Tshz1神经元一旦激活就会引起厌恶、运动抑制和负强化，并且它们会接收一组不同的突触输入。这些神经元主要是受到惩罚而不是奖励而兴奋，并代表对惩罚的预期或逃避的动机。此外，抑制这些神经元会损害基于惩罚的学习，而不会影响奖励学习或运动。这些结果确立了纹状体神经元在受惩罚强化的行为中的主要作用，此外还揭示了经典模型中未解释的直接途径的功能。