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

Hendrik Heiser, Filippo Kiessler, Adrian Roggenbach, Victor Ibanez, Martin Wieckhorst, Fritjof Helmchen, Julijana Gjorgjieva and Anna-Sophia Wahl ()
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Hendrik Heiser: University of Zurich
Filippo Kiessler: Technical University of Munich
Adrian Roggenbach: University of Zurich
Victor Ibanez: University of Zurich
Martin Wieckhorst: University of Zurich
Fritjof Helmchen: University of Zurich
Julijana Gjorgjieva: Technical University of Munich
Anna-Sophia Wahl: University of Zurich

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-58688-4

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