In a delayed alternation spatial working memory task, hippocampal time cells fire during specific moments of the delay period to form a stable, sequential representation of the entire delay interval. The causal relationship between these sequences and working memory remains unclear. Similarly, hippocampal theta oscillations are thought to support working memory, primarily through the generation of time cell sequences. To causally examine these relationships, we optogenetically silenced the medial septal GABAergic theta-generating circuit during the delay portion of a delayed spatial alternation task. Without hippocampal theta oscillations, many time cells exhibited remapping, new time cells were recruited, and time cell information was increased; collectively resulting in a new time cell sequence during the delay period. Despite this remapping of time cells on random selection of theta-reduced trials, behavioral performance was unimpaired, demonstrating that working memory is not dependent on a single or unique time cell sequence during the delay period.

The neural mechanisms behind the role of rapid-eye-movement sleep (REMs) in spatial memory formation are unclear. Here, we performed hippocampal CA1 single-unit recordings in mice expressing archaerhodopsin in GABAergic neurons of the medial septum (MSGABA), an established optogenetic method enabling REMs-selective theta rhythm attenuation resulting in spatial memory deficits. Analysis of CA1 neural assemblies during REMs revealed reduced synchrony of constituent neural activity during MSGABA silencing. Subsequent investigation of recently formed CA1 place cells demonstrated that REMs-selective MSGABA inhibition reduced the place stability of those which participated in prior REMs assembly activity, but not of those which did not. This suggests that CA1 neural assemblies during REMs facilitate spatial memory formation by stabilizing spatial representations in a plastic subpopulation of participating CA1 neurons.