Neural correlates of position, progress, and action during reward-guided sequence navigation in the rat medial prefrontal cortex

The complexity surrounding the seamless execution of skilled action sequences during sparse rewards necessitates an organization of behavior into modular, temporally extended sub-policies. The rodent Medial Prefrontal Cortex (mPFC) has emerged as a critical brain region implicated in orchestrating such action plans over extended time frames. Previous research has shed light on the mPFC’s mechanistic contributions to the control of behavior through investigations into its numerous attributed roles, encompassing working memory, spatial representation, decision-making, and task-specific generalization. We investigated the neural correlates of position, task-specific features, and actions within the rat mPFC during a behaviorally elaborate, reward-guided sequence navigation paradigm. We identified a significant proportion of mPFC neurons exhibiting a robust task-specific code for tracking animal’s progress between rewards, characterized most prominently by modulation departures from and approaches to reward zones. Furthermore, initial population-level analyses suggested a representation of prospective non-immediate actions, encoded as turn directions, extending beyond immediate temporal horizons. However, subsequent in-depth examination revealed that these initial findings could not hold up to predict future actions at single-trial level. Instead, the apparent prospective coding of turn directions seemed to be confounded by preparatory motor behaviors within the navigational environment. Consequently, these results call for a reassessment of the influence of various sensorimotor factors on mPFC activity during goal-directed decision-making, challenging the prevailing methodologies used to infer cognitive processes within this region.