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  • Spatial Coding Dysfunction and Network Instability in the Aging Medial Entorhinal Cortex. bioRxiv : the preprint server for biology Herber, C. S., Pratt, K. J., Shea, J. M., Villeda, S. A., Giocomo, L. M. 2024

    Abstract

    Across species, spatial memory declines with age, possibly reflecting altered hippocampal and medial entorhinal cortex (MEC) function. However, the integrity of cellular and network-level spatial coding in aged MEC is unknown. Here, we leveraged in vivo electrophysiology to assess MEC function in young, middle-aged, and aged mice navigating virtual environments. In aged grid cells, we observed impaired stabilization of context-specific spatial firing, correlated with spatial memory deficits. Additionally, aged grid networks shifted firing patterns often but with poor alignment to context changes. Aged spatial firing was also unstable in an unchanging environment. In these same mice, we identified 458 genes differentially expressed with age in MEC, 61 of which had expression correlated with spatial firing stability. These genes were enriched among interneurons and related to synaptic transmission. Together, these findings identify coordinated transcriptomic, cellular, and network changes in MEC implicated in impaired spatial memory in aging.

    View details for DOI 10.1101/2024.04.12.588890

    View details for PubMedID 38659809

    View details for PubMedCentralID PMC11042240