Abstract

Recently microglia, the resident immune cells of the brain, have been recognized as multi-tasking talents that are not only essential in the diseased brain, but also actively contribute to synaptic circuit remodeling during normal brain development. It is well established that microglia dynamically scan their environment and thereby establish transient physical contacts with neuronal synapses, which may allow them to sense and influence synaptic function. However, it is unknown whether and how the morphological dynamics of microglia and their physical interactions with synapses are affected by the induction of synaptic plasticity in the adult brain. To this end, we characterized the morphological dynamics of microglia and their interactions with synapses before and after the induction of synaptic plasticity (LTP) in the hippocampus by time-lapse two-photon imaging and electrophysiological recordings in acute brain slices. We demonstrate that during hippocampal LTP microglia alter their morphological dynamics by increasing the number of their processes and by prolonging their physical contacts with dendritic spines. These effects were absent in the presence of an NMDA receptor antagonist. Taken together, this altered behavior could reflect an active microglial involvement in circuit remodeling during activity-dependent synaptic plasticity in the healthy adult brain.

Highlights

  • Given these incongruent reports, we set out to revisit this issue by directly visualizing the morphological interactions between microglial processes and dendritic spines during synaptic plasticity

  • To investigate whether microglia can sense the induction of synaptic plasticity, we compared microglial morphological dynamics before and after the induction of LTP in hippocampal CA1, which was robustly expressed after electrical high-frequency stimulation (HFS) of the Schaffer collateral afferents (161.6% ± 1.1% of baseline, n = 10 slices, p < 0.001; Fig. 1C)

  • We have shown that microglia establish transient contacts with a sizable fraction of dendritic spines within a relatively short period of time under baseline conditions in healthy adult brain tissue

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Summary

Introduction

We set out to revisit this issue by directly visualizing the morphological interactions between microglial processes and dendritic spines during synaptic plasticity. To this end, we combined two-photon time-lapse imaging with extracellular field recordings in acute hippocampal brain slices obtained from transgenic mice, where microglia and neurons were labeled by two different fluorophores. We analyzed the morphological dynamics of microglia and their dynamic interactions with dendritic spines of CA1 pyramidal neurons before and after the induction of hippocampal LTP. Our study provides clear evidence for microglia to be able to sense and react to the induction of synaptic plasticity, supporting the notion of a microglial contribution to activity-dependent changes at the synapse in the healthy adult brain

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