Microglial motility is modulated by neuronal activity and correlates with dendritic spine plasticity in the hippocampus of awake mice

Abstract

Microglia, the resident immune cells of the brain, play a complex role in health and disease. They actively survey the brain parenchyma by physically interacting with other cells and structurally shaping the brain. Yet the mechanisms underlying microglial motility and significance for synapse stability, especially in the hippocampus during adulthood, remain widely unresolved. Here we investigated the effect of neuronal activity on microglial motility and the implications for the formation and survival of dendritic spines on hippocampal CA1 neurons in vivo. We used repetitive two-photon in vivo imaging in the hippocampus of awake and anesthetized mice to simultaneously study the motility of microglia and their interaction with dendritic spines. We found that CA3 to CA1 input is sufficient to modulate microglial process motility. Simultaneously, more dendritic spines emerged in mice after awake compared to anesthetized imaging. Interestingly, the rate of microglial contacts with individual dendritic spines and dendrites was associated with the stability, removal, and emergence of dendritic spines. These results suggest that microglia might sense neuronal activity via neurotransmitter release and actively participate in synaptic rewiring of the hippocampal neural network during adulthood. Further, this study has profound relevance for hippocampal learning and memory processes.

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Article and author information

Author details

  1. Felix Christopher Nebeling

    Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases, Bonn, Germany
    For correspondence
    felix.nebeling@dzne.de
    Competing interests
    The authors declare that no competing interests exist.
  2. Stefanie Poll

    Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5301-2791
  3. Lena Christine Schmid

    Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Julia Steffen

    Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Kevin Keppler

    Light Microscopy Facility, German Center for Neurodegenerative Diseases, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Manuel Mittag

    Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Martin Fuhrmann

    Neuroimmunology and Imaging Group, German Center for Neurodegenerative Diseases, Bonn, Germany
    For correspondence
    martin.fuhrmann@dzne.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7672-2913

Funding

European Research Council (865618)

  • Manuel Mittag
  • Martin Fuhrmann

Deutsche Forschungsgemeinschaft (SFB1089,C01)

  • Stefanie Poll
  • Martin Fuhrmann

Deutsche Forschungsgemeinschaft (SFB1089,B06)

  • Julia Steffen
  • Martin Fuhrmann

Deutsche Forschungsgemeinschaft (SPP2395)

  • Martin Fuhrmann

ERA-NET NEURON (MicroSynDep)

  • Felix Christopher Nebeling
  • Martin Fuhrmann

ERA-NET NEURON (MicroSchiz)

  • Felix Christopher Nebeling
  • Stefanie Poll
  • Martin Fuhrmann

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Laura L Colgin, University of Texas at Austin, United States

Ethics

Animal experimentation: This and all procedures described were in accordance with the intern regulations of the DZNE and animal experimental protocols approved by the government of North Rhine Westphalia (84-02.04.2017.A098).

Version history

  1. Preprint posted: January 10, 2019 (view preprint)
  2. Received: September 1, 2022
  3. Accepted: February 3, 2023
  4. Accepted Manuscript published: February 7, 2023 (version 1)
  5. Version of Record published: February 22, 2023 (version 2)

Copyright

© 2023, Nebeling et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Felix Christopher Nebeling
  2. Stefanie Poll
  3. Lena Christine Schmid
  4. Julia Steffen
  5. Kevin Keppler
  6. Manuel Mittag
  7. Martin Fuhrmann
(2023)
Microglial motility is modulated by neuronal activity and correlates with dendritic spine plasticity in the hippocampus of awake mice
eLife 12:e83176.
https://doi.org/10.7554/eLife.83176

Share this article

https://doi.org/10.7554/eLife.83176

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