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

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 i...

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Main Authors: Hendrik Heiser, Filippo Kiessler, Adrian Roggenbach, Victor Ibanez, Martin Wieckhorst, Fritjof Helmchen, Julijana Gjorgjieva, Anna-Sophia Wahl
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58688-4
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author Hendrik Heiser
Filippo Kiessler
Adrian Roggenbach
Victor Ibanez
Martin Wieckhorst
Fritjof Helmchen
Julijana Gjorgjieva
Anna-Sophia Wahl
author_facet Hendrik Heiser
Filippo Kiessler
Adrian Roggenbach
Victor Ibanez
Martin Wieckhorst
Fritjof Helmchen
Julijana Gjorgjieva
Anna-Sophia Wahl
author_sort Hendrik Heiser
collection DOAJ
description 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.
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spelling doaj-art-bcaa4b5c1b1c42a5a40bdd09aa5d52942025-08-20T02:28:04ZengNature PortfolioNature Communications2041-17232025-04-0116111710.1038/s41467-025-58688-4Brain-wide microstrokes affect the stability of memory circuits in the hippocampusHendrik Heiser0Filippo Kiessler1Adrian Roggenbach2Victor Ibanez3Martin Wieckhorst4Fritjof Helmchen5Julijana Gjorgjieva6Anna-Sophia Wahl7Brain Research Institute, University of ZurichSchool of Life Sciences, Technical University of MunichBrain Research Institute, University of ZurichBrain Research Institute, University of ZurichBrain Research Institute, University of ZurichBrain Research Institute, University of ZurichSchool of Life Sciences, Technical University of MunichBrain Research Institute, University of ZurichAbstract 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.https://doi.org/10.1038/s41467-025-58688-4
spellingShingle Hendrik Heiser
Filippo Kiessler
Adrian Roggenbach
Victor Ibanez
Martin Wieckhorst
Fritjof Helmchen
Julijana Gjorgjieva
Anna-Sophia Wahl
Brain-wide microstrokes affect the stability of memory circuits in the hippocampus
Nature Communications
title Brain-wide microstrokes affect the stability of memory circuits in the hippocampus
title_full Brain-wide microstrokes affect the stability of memory circuits in the hippocampus
title_fullStr Brain-wide microstrokes affect the stability of memory circuits in the hippocampus
title_full_unstemmed Brain-wide microstrokes affect the stability of memory circuits in the hippocampus
title_short Brain-wide microstrokes affect the stability of memory circuits in the hippocampus
title_sort brain wide microstrokes affect the stability of memory circuits in the hippocampus
url https://doi.org/10.1038/s41467-025-58688-4
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