The prefrontal cortex (PFC) plays a critical role in curbing impulsive behavior, but the underlying circuit mechanism remains incompletely understood. Here we show that a subset of dorsomedial PFC (dmPFC) layer 5 pyramidal neurons, which project to the subthalamic nucleus (STN) of the basal ganglia, play a key role in inhibiting impulsive responses in a go/no-go task. Projection-specific labeling and calcium imaging showed that the great majority of STN-projecting neurons were preferentially active in no-go trials when the mouse successfully withheld licking responses, but lateral hypothalamus (LH)-projecting neurons were more active in go trials with licking; visual cortex (V1)-projecting neurons showed only weak task-related activity. Optogenetic activation and inactivation of STN-projecting neurons reduced and increased inappropriate licking, respectively, partly through their direct innervation of the STN, but manipulating LH-projecting neurons had the opposite effects. These results identify a projection-defined subtype of PFC pyramidal neurons as key mediators of impulse control.

前额叶皮层（PFC）在抑制冲动行为方面起着至关重要的作用，但其潜在的电路机制仍不完全清楚。在这里，我们显示了背突PFC（dmPFC）第5层锥体神经元的子集，该子集投射到基底神经节的丘脑下核（STN），在抑制执行/不执行任务的冲动反应中起关键作用。投射特异性标记和钙成像显示，当小鼠成功地保持舔ing反应时，绝大多数STN投射神经元在无用试验中均具有优先活性，而外侧下丘脑（LH）投射神经元在进行舔go的试验中更为活跃; 视觉皮层（V1）投影神经元显示仅与任务相关的活动较弱。投射STN的神经元的光遗传激活和失活减少和增加了不适当的舔ing，分别部分地是通过它们直接支配STN，但是操纵LH投射神经元却产生了相反的效果。这些结果确定了PFC锥体神经元的投影定义亚型作为冲动控制的关键介体。