Samuel J Levy, Nathaniel R Kinsky, William Mau, David W Sullivan, Michael E Hasselmo. Hippocampal spatial memory representations in mice are heterogeneously stable. bioRxiv 843037; doi: https://doi.org/10.1101/843037

Abstract
“The population of hippocampal neurons actively coding space continually changes across days as mice repeatedly perform tasks. Many hippocampal place cells become inactive while other previously silent neurons become active, challenging the belief that stable behaviors and memory representations are supported by stable patterns of neural activity. Active cell replacement may disambiguate unique episodes that contain overlapping memory cues, and could contribute to reorganization of memory representations. How active cell replacement affects the evolution of representations of different behaviors within a single task is unknown. We trained mice to perform a Delayed Non-Match to Place (DNMP) task over multiple weeks, and performed calcium imaging in area CA1 of the dorsal hippocampus using head-mounted miniature microscopes. Cells active on the central stem of the maze “split” their calcium activity according to the animal’s upcoming turn direction (left or right), the current task phase (study or test), or both task dimensions, even while spatial cues remained unchanged. We found that different splitter neuron populations were replaced at unequal rates, resulting in an increasing number of cells modulated by turn direction and a decreasing number of cells with combined modulation by both turn direction and task phase. Despite continual reorganization, the ensemble code stably segregated these task dimensions. These results show that hippocampal memories can heterogeneously reorganize even while behavior is unchanging.“

Significance statement

“Single photon calcium imaging using head-mounted miniature microscopes in freely moving animals, has enabled researchers to measure the long term stability of hippocampal pyramidal cells during repeated behaviors. Previous studies have demonstrated instability of neural circuit components including dendritic spines and axonal boutons. It is now known that single units in the neuronal population exhibiting behaviorally relevant activity eventually become inactive and that previously silent neurons can quickly acquire task-relevant activity. The function of such population dynamics is unknown. We show here that population dynamics differ for cells coding distinct task dimensions, suggesting such dynamics are part of a mechanism for latent memory reorganization. These results add to a growing body of work showing that maintenance of episodic memory is an ongoing and dynamic process.”

Samuel J Levy, Nathaniel R Kinsky, William Mau, David W Sullivan, Michael E Hasselmo. Hippocampal spatial memory representations in mice are heterogeneously stable. bioRxiv 843037; doi: https://doi.org/10.1101/843037