Formation of Task Representations and Replay in Mouse Medial Prefrontal Cortex

The medial prefrontal cortex (mPFC) is thought to support cognitive flexibility by forming and maintaining generalized representations of abstract tasks. The formation of these representations as well as their relation to preexisting representations of contextual or spatial information is incompletely understood. In this study, we analyzed longitudinal 1-photon calcium recordings in mice performing an olfaction-guided spatial memory task over an eight-week period that included habituation, training, and sleep epochs. Our results reveal that, while a minority of neurons initially conveyed significant information about the behavior of the animal, the bulk of task-related activity only emerged after the animals reached proficient performance. Although goal arm information is robustly represented at both the single-cell and network levels both during learning and in task proficient mice, it undergoes significant remapping throughout the learning process. Additionally, we identified the establishment of recurring sequences during learning and their replay at reward locations, with no evidence of them existing during odor sampling phase, during sleep or before training. These findings suggest that the mPFC predominantly establishes generalized task representations de novo during learning, relying only minimally on preexisting spatial representations and that sub-second neural sequences in the mPFC are more likely involved in evaluating behavioral outcomes rather than planning future actions.