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Neuron DOI:10.1016/j.neuron.2018.09.017

CD47 Protects Synapses from Excess Microglia-Mediated Pruning during Development.

Publication TypeJournal Article
Year of Publication2018
AuthorsLehrman, EK, Wilton, DK, Litvina, EY, Welsh, CA, Chang, ST, Frouin, A, Walker, AJ, Heller, MD, Umemori, H, Chen, C, Stevens, B
JournalNeuron
Volume100
Issue1
Pages120-134.e6
Date Published2018 Oct 10
ISSN1097-4199
Abstract

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.

DOI10.1016/j.neuron.2018.09.017
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/30308165?dopt=Abstract

Alternate JournalNeuron
PubMed ID30308165
PubMed Central IDPMC6314207
Grant ListR01 EY013613 / EY / NEI NIH HHS / United States
P30 HD018655 / HD / NICHD NIH HHS / United States
R01 MH111647 / MH / NIMH NIH HHS / United States
U54 HD090255 / HD / NICHD NIH HHS / United States
R01 NS071008 / NS / NINDS NIH HHS / United States
R01 NS092578 / NS / NINDS NIH HHS / United States