Optogenetic reduction of theta oscillations reveals that a single reliable time cell sequence is not required for working memory

Abstract

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.