Inhibition of impulsive action by projection-defined prefrontal pyramidal neurons

Significance The prefrontal cortex (PFC) has long been recognized as a crucial region for suppressing impulsive behavior, but the specific neurons mediating the effect remained elusive. Using projection-specific labeling of PFC neurons for imaging and optogenetic manipulation in mice performing a go/no-go task, we showed that the subset of layer 5 pyramidal neurons projecting to the subthalamic nucleus, but not those projecting to the lateral hypothalamus or visual cortex, play a critical role in inhibiting impulsive responses. Our demonstration of a distinct functional property of a projection-defined PFC pyramidal neuron population provides an important entry point for delineating the PFC circuit underlying impulse control.