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Microglia-astrocyte crosstalk regulates synapse remodeling via Wnt signaling [preprint]

Faust, Travis E
Lee, Yi-Han
O'Connor, Ciara
Boyle, Margaret A
Gunner, Georgia
Badimon, Ana
Ayata, Pinar
Schaefer, Anne
Schafer, Dorothy P
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Abstract

Astrocytes and microglia are emerging key regulators of activity-dependent synapse remodeling that engulf and remove synapses in response to changes in neural activity. Yet, the degree to which these cells communicate to coordinate this process remains an open question. Here, we use whisker removal in postnatal mice to induce activity-dependent synapse removal in the barrel cortex. We show that astrocytes do not engulf synapses in this paradigm. Instead, astrocytes reduce their contact with synapses prior to microglia-mediated synapse engulfment. We further show that reduced astrocyte-contact with synapses is dependent on microglial CX3CL1-CX3CR1 signaling and release of Wnts from microglia following whisker removal. These results demonstrate an activity-dependent mechanism by which microglia instruct astrocyte-synapse interactions, which then provides a permissive environment for microglia to remove synapses. We further show that this mechanism is critical to remodel synapses in a changing sensory environment and this signaling is upregulated in several disease contexts.

Source

Faust TE, Lee YH, O'Connor CD, Boyle MA, Gunner G, Badimon A, Ayata P, Schaefer A, Schafer DP. Microglia-astrocyte crosstalk regulates synapse remodeling via Wnt signaling. bioRxiv [Preprint]. 2024 Feb 9:2024.02.08.579178. doi: 10.1101/2024.02.08.579178. PMID: 38370645; PMCID: PMC10871360.

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10.1101/2024.02.08.579178
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38370645
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This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.Attribution 4.0 International