Microglia regulate synaptic circuit remodeling and phagocytose synaptic material in the healthy brain; however, the mechanisms directing microglia to engulf specific synapses and avoid others remain unknown. Here, we demonstrate that an innate immune signaling pathway protects synapses from inappropriate removal. The expression patterns of CD47 and its receptor, SIRPα, correlated with peak pruning in the developing retinogeniculate system, and mice lacking these proteins exhibited increased microglial engulfment of retinogeniculate inputs and reduced synapse numbers in the dorsal lateral geniculate nucleus. CD47-deficient mice also displayed increased functional pruning, as measured by electrophysiology. In addition, CD47 was found to be required for neuronal activity-mediated changes in engulfment, as microglia in CD47 knockout mice failed to display preferential engulfment of less active inputs. Taken together, these results demonstrate that CD47-SIRPα signaling prevents excess microglial phagocytosis and show that molecular brakes can be regulated by activity to protect specific inputs.
Pubmed ID: 30308165 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets VGLUT1
View all literature mentionsThis monoclonal targets Neuronal Class III beta-Tubulin (TUJ1) Purified
View all literature mentionsThis polyclonal targets Iba1
View all literature mentionsThis monoclonal targets NR1
View all literature mentionsThis monoclonal targets RAT ANTI MOUSE CD11b
View all literature mentionsThis polyclonal targets Synapsin 1
View all literature mentionsThis monoclonal targets Post Synaptic Density Protein 95 (PSD-95)
View all literature mentionsThis unknown targets Human SIRP alpha (CT)
View all literature mentionsThis polyclonal targets VGluT2
View all literature mentionsThis monoclonal targets CD47
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis polyclonal targets Fluorescein
View all literature mentionsThis polyclonal targets Digoxigenin
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsAllele Detail: Targeted, Transgenic This is a legacy resource.
View all literature mentionsMus musculus with name B6.129S7-Cd47tm1Fpl/J from IMSR.
View all literature mentionsThis polyclonal targets Synapsin 1
View all literature mentionsThis monoclonal targets Post Synaptic Density Protein 95 (PSD-95)
View all literature mentionsThis monoclonal targets Neuronal Class III beta-Tubulin (TUJ1) Purified
View all literature mentionsThis polyclonal targets VGluT2
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis polyclonal targets VGLUT1
View all literature mentionsThis unknown targets Human SIRP alpha (CT)
View all literature mentionsThis monoclonal targets CD47
View all literature mentionsThis monoclonal targets NR1
View all literature mentionsThis monoclonal targets RAT ANTI MOUSE CD11b
View all literature mentions