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
Citations
Student Authors
Faculty Advisor
Academic Program
Document Type
Publication Date
Keywords
Subject Area
Embargo Expiration Date
Link to Full Text
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.
Year of Medical School at Time of Visit
Sponsors
Dates of Travel
DOI
Permanent Link to this Item
PubMed ID
Other Identifiers
Notes
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.