Hippocampal theta sequences in REM sleep during spatial learning

Abstract

Rapid eye movement (REM) sleep is known to play a role in hippocampally-dependent memory, yet the activity and development of hippocampal neuronal ensembles during this state is not well understood. Here we investigated patterning of CA1 place cell activity by theta oscillations, a shared electrophysiological hallmark of both waking behavior and REM sleep, in male rats learning a spatial memory task. We report the existence of REM theta sequences, sequential reactivations of place cells in REM theta that parallel waking theta sequences. REM and wake theta sequences develop rapidly with experience, recapitulating behavioral sequences of compressed space in forward and reverse directions throughout learning. REM sleep exhibited a balance of forward and reverse sequences in contrast to predominantly forward wake theta sequences. Finally, we found that a CA1 neuronal population known to shift preferred theta phases in REM exhibited differential participation in wake and REM theta sequences. In particular, this phase-shifting population showed an increased contribution to REM theta sequence representations after behavioral performance asymptotes and the task is learned, supporting a previously hypothesized role in depotentiation. These findings suggest a role for REM associated theta sequences in state dependent memory functions of the hippocampal circuit, providing evidence that REM sleep is associated with sequence reactivation that can support consolidation of representations necessary for memory guided behavior.