Distinct roles of prefrontal cortex neurons in set shifting

Cognitive flexibility, the ability to adjust behavioral strategies in response to changing environmental contingencies, requires adaptive processing of internal states and contextual cues to guide goal-oriented behavior, and is dependent on prefrontal cortex (PFC) functions. However, the neurophysiological underpinning of how the PFC supports cognitive flexibility is not well understood and has been under active investigation. We recorded spiking activity from single PFC neurons in mice performing the attentional set-shifting task, where mice learned to associate different contextually relevant sensory stimuli to reward. We identified subgroups of PFC neurons encoding task context, choice and trial outcome. Putative fast-spiking neurons were more involved in representing outcome and choice than putative regular-spiking neurons. Regression model further revealed that task context and trial outcome modulated the activity of choice-encoding neurons in rule-dependent and cell type-dependent manners. Together, our data provide new evidence to elucidate PFC’s role in cognitive flexibility, suggesting differential cell type-specific engagement during set shifting, and that both contextual rule representation and trial outcome monitoring underlie PFC’s unique capacity to support flexible behavioral switching.