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Brain-wide microstrokes affect the stability of memory circuits in the hippocampus

Author

Listed:
  • Hendrik Heiser

    (University of Zurich
    University of Zurich)

  • Filippo Kiessler

    (Technical University of Munich)

  • Adrian Roggenbach

    (University of Zurich
    University of Zurich)

  • Victor Ibanez

    (University of Zurich
    University of Zurich)

  • Martin Wieckhorst

    (University of Zurich
    University of Zurich)

  • Fritjof Helmchen

    (University of Zurich
    University of Zurich
    University of Zurich)

  • Julijana Gjorgjieva

    (Technical University of Munich)

  • Anna-Sophia Wahl

    (University of Zurich
    University of Zurich
    LMU Munich
    Ludwigs-Maximilians-University)

Abstract

Cognitive deficits affect over 70% of stroke survivors, yet the mechanisms by which multiple small ischemic events contribute to cognitive decline remain poorly understood. In this study, we employed chronic two-photon calcium imaging to longitudinally track the fate of individual neurons in the hippocampus of mice navigating a virtual reality environment, both before and after inducing brain-wide microstrokes. Our findings reveal that, under normal conditions, hippocampal neurons exhibit varying degrees of stability in their spatial memory coding. However, microstrokes disrupted this functional network architecture, leading to cognitive impairments. Notably, the preservation of stable coding place cells, along with the stability, precision, and persistence of the hippocampal network, was strongly predictive of cognitive outcomes. Mice with more synchronously active place cells near important locations demonstrated recovery from cognitive impairment. This study uncovers critical cellular responses and network alterations following brain injury, providing a foundation for novel therapeutic strategies preventing cognitive decline.

Suggested Citation

  • Hendrik Heiser & Filippo Kiessler & Adrian Roggenbach & Victor Ibanez & Martin Wieckhorst & Fritjof Helmchen & Julijana Gjorgjieva & Anna-Sophia Wahl, 2025. "Brain-wide microstrokes affect the stability of memory circuits in the hippocampus," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58688-4
    DOI: 10.1038/s41467-025-58688-4
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    References listed on IDEAS

    as
    1. Christine Grienberger & Jeffrey C. Magee, 2022. "Entorhinal cortex directs learning-related changes in CA1 representations," Nature, Nature, vol. 611(7936), pages 554-562, November.
    2. Christine Grienberger & Jeffrey C. Magee, 2022. "Author Correction: Entorhinal cortex directs learning-related changes in CA1 representations," Nature, Nature, vol. 612(7938), pages 8-8, December.
    3. Wolfgang Omlor & Anna-Sophia Wahl & Pia Sipilä & Henry Lütcke & Balazs Laurenczy & I-Wen Chen & Lazar T. Sumanovski & Marcel van ’t Hoff & Philipp Bethge & Fabian F. Voigt & Martin E. Schwab & Fritjof, 2019. "Context-dependent limb movement encoding in neuronal populations of motor cortex," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    4. Thomas Hainmueller & Marlene Bartos, 2018. "Parallel emergence of stable and dynamic memory engrams in the hippocampus," Nature, Nature, vol. 558(7709), pages 292-296, June.
    5. A. S. Wahl & U. Büchler & A. Brändli & B. Brattoli & S. Musall & H. Kasper & B. V. Ineichen & F. Helmchen & B. Ommer & M. E. Schwab, 2017. "Optogenetically stimulating intact rat corticospinal tract post-stroke restores motor control through regionalized functional circuit formation," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
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