(The) functional significance of prefrontal cortex cell types in flexible behavioral control

Abstract

The prefrontal cortex (PFC) plays a crucial role in flexible control of behavior. To investigate contributions of different PFC cell types to behavioral flexibility, I focused on vasoactive intestinal peptide (VIP)-expressing neurons, known to exert a powerful disinhibitory influence on the cortical circuit, and two major types of pyramidal neurons, intratelencephalic (IT) and pyramidal tract (PT) projection neurons in the layer 5. I trained mice to perform a probabilistic reversal learning task under a classical conditioning paradigm, in which distinct odor cues were associated with either a drop of water (reward) or an air puff (punishment) each with $75%$ probability. Manipulating the activity of VIP or PT neurons, but not IT neurons, impaired reversal learning. All types of cells showed a diverse array of responses during classical conditioning, as well as heterogeneous dynamics during reversal. IT and PT neurons carried strong signals related to task state and expected outcome, respectively. VIP neurons detected the onset of reversal and conveyed strong signals related to reward prediction error during behavioral reversal, but not before or after. Moreover, this signal’s persistence across trials correlated with the reversal learning speed. Overall, these results suggest the VIP neuronal role in detecting significant deviations from ongoing environmental contingency and imposing error-correction signals, while the PT neuronal role in transmitting expected outcome signals to subcortical brain regions, facilitating rapid behavioral adjustments. This work provides novel perspectives on prefrontal cortical neural processes underlying flexible behavioral control.