Multiple time-scales of decision-making in the hippocampus and prefrontal cortex

The prefrontal cortex and hippocampus are crucial for memory-guided decision-making. Neural activity in the hippocampus exhibits place-cell sequences at multiple timescales, including slow behavioral sequences (~seconds) and fast theta sequences (~100–200 ms) within theta oscillation cycles. How prefrontal ensembles interact with hippocampal sequences to support decision-making is unclear. Here, we examined simultaneous hippocampal and prefrontal ensemble activity in rats during learning of a spatial working-memory decision task. We found clear theta sequences in prefrontal cortex, nested within its behavioral sequences. In both regions, behavioral sequences maintained representations of current choices during navigation. In contrast, hippocampal theta sequences encoded alternatives for deliberation and were coordinated with prefrontal theta sequences that predicted upcoming choices. During error trials, these representations were preserved to guide ongoing behavior, whereas replay sequences during inter-trial periods were impaired prior to navigation. These results establish cooperative interaction between hippocampal and prefrontal sequences at multiple timescales for memory-guided decision-making.