Prefrontal Cortical Neurons Are Selective for Non-Local Hippocampal Representations during Replay and Behavior

Diverse functions such as decision-making and memory consolidation may depend on communication between neurons in the hippocampus (HP) and prefrontal cortex (PFC). HP replay is a candidate mechanism to facilitate this communication, however details remain largely unknown because of the technical challenges of recording sufficient numbers of HP neurons for replay while also recording PFC neurons. Here, we implanted male rats with 40-tetrode drives, split between HP and PFC, during learning of a Y-maze spatial memory task. Surprisingly, we found that in contrast to their non-selectivity for maze arm during movement, a portion of PFC neurons were highly selective for HP replay of different arms. Moreover, PFC neurons' selectivity to HP non-local arm representation during running tended to match their replay arm selectivity and was predictive of future choice. Thus, PFC activity that is tuned to HP activity is best explained by non-local HP position representations rather than HP representation of actual position, providing a new potential mechanism of HP-PFC coordination during HP replay.SIGNIFICANCE STATEMENT The hippocampus (HP) is implicated in spatial learning while the prefrontal cortex (PFC) is implicated in decision-making. The question of how the two areas interact has been of great interest. A specific activity type in HP called replay is particularly interesting because it resembles internal exploration of non-local experiences, but is technically challenging to study, requiring recordings from large numbers of HP neurons simultaneously. Here, we combined replay recordings from HP with prefrontal recordings, to reveal a surprising degree of selectivity for replay, and a pattern of coordination that supports some conceptions of hippocampocortical interaction and challenges others.