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Spatial coding dysfunction and network instability in the aging medial entorhinal cortex

Author

Listed:
  • Charlotte S. Herber

    (Stanford University School of Medicine)

  • Karishma J. B. Pratt

    (University of California San Francisco)

  • Jeremy M. Shea

    (University of California San Francisco)

  • Saul A. Villeda

    (University of California San Francisco
    Bakar Aging Research Institute)

  • Lisa M. Giocomo

    (Stanford University School of Medicine
    Stanford University School of Medicine)

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 coding quality. These genes were interneuron-enriched and related to synaptic plasticity, notably including a perineuronal net component. Together, these findings identify coordinated transcriptomic, cellular, and network changes in MEC implicated in impaired spatial memory in aging.

Suggested Citation

  • Charlotte S. Herber & Karishma J. B. Pratt & Jeremy M. Shea & Saul A. Villeda & Lisa M. Giocomo, 2025. "Spatial coding dysfunction and network instability in the aging medial entorhinal cortex," Nature Communications, Nature, vol. 16(1), pages 1-27, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63229-0
    DOI: 10.1038/s41467-025-63229-0
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