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.
Data availability
Data related to the manuscript are available according to the FAIR principles via Dryad
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Data from: Microglial motility is modulated by neuronal activity and correlates with dendritic spine plasticity in the hippocampus of awake miceDryad Digital Repository, doi:10.5061/dryad.63xsj3v68.
Article and author information
Author details
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
- 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
- Preprint posted: January 10, 2019 (view preprint)
- Received: September 1, 2022
- Accepted: February 3, 2023
- Accepted Manuscript published: February 7, 2023 (version 1)
- 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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