{'fraction_non_alphanumeric': 0.024986985944820406, 'fraction_numerical': 0.0015616866215512754, 'mean_word_length': 5.673611111111111, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
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. 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.