Cue-responsive mPFC neuronal populations are associated with response execution and response withholding in a...

Response inhibition is an important component of behavioral control that enables organisms to withhold inappropriate or prepotent responses under specific environmental contingencies. The prefrontal cortex (PFC) has been widely implicated in this process, yet how populations of PFC neurons are differentially recruited during response withholding and response execution remains incompletely understood. In this study, rats were trained on a Go/No-Go task, and calcium activity in medial PFC (mPFC) pyramidal neurons was monitored using a miniscope during freely behaving performance. The results revealed that distinct cue-responsive populations of mPFC pyramidal neurons were associated with Go and No-Go conditions, with both increased and decreased calcium activity observed following the corresponding auditory cues. Some neurons exhibited transient cue-related activity, whereas others showed more sustained or temporally distributed activity during the defined response-withholding period. Some neurons exhibited transient cue-related activity, whereas others showed more sustained or temporally distributed activity during the defined response-withholding period. Notably, subsets of neurons responded to both Go and No-Go cues, indicating overlapping as well as cue-dependent response profiles across task conditions. At the population level, cue-responsive neuronal populations showed associations with behavioral outcome. However, these functionally defined populations do not establish specific co-active neuronal populations or causal contributions to behavior. Together, these findings provide a population-level characterization of mPFC neuronal dynamics associated with response withholding and response execution and highlight the heterogeneous and cue-dependent organization of prefrontal activity during behavioral control.