Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner

Dorothy P. Schafer, Emily K. Lehrman, Amanda G. Kautzman, Ryuta Koyama, Alan R. Mardinly, Ryo Yamasaki, Richard M. Ransohoff, Michael E. Greenberg, Ben A. Barres, Beth Stevens

Research output: Contribution to journalArticle

1178 Citations (Scopus)

Abstract

Microglia are the resident CNS immune cells and active surveyors of the extracellular environment. While past work has focused on the role of these cells during disease, recent imaging studies reveal dynamic interactions between microglia and synaptic elements in the healthy brain. Despite these intriguing observations, the precise function of microglia at remodeling synapses and the mechanisms that underlie microglia-synapse interactions remain elusive. In the current study, we demonstrate a role for microglia in activity-dependent synaptic pruning in the postnatal retinogeniculate system. We show that microglia engulf presynaptic inputs during peak retinogeniculate pruning and that engulfment is dependent upon neural activity and the microglia-specific phagocytic signaling pathway, complement receptor 3(CR3)/C3. Furthermore, disrupting microglia-specific CR3/C3 signaling resulted in sustained deficits in synaptic connectivity. These results define a role for microglia during postnatal development and identify underlying mechanisms by which microglia engulf and remodel developing synapses.

Original languageEnglish
Pages (from-to)691-705
Number of pages15
JournalNeuron
Volume74
Issue number4
DOIs
Publication statusPublished - May 24 2012
Externally publishedYes

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Microglia
Macrophage-1 Antigen
Synapses
Neuronal Plasticity
Brain

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., ... Stevens, B. (2012). Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner. Neuron, 74(4), 691-705. https://doi.org/10.1016/j.neuron.2012.03.026

Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner. / Schafer, Dorothy P.; Lehrman, Emily K.; Kautzman, Amanda G.; Koyama, Ryuta; Mardinly, Alan R.; Yamasaki, Ryo; Ransohoff, Richard M.; Greenberg, Michael E.; Barres, Ben A.; Stevens, Beth.

In: Neuron, Vol. 74, No. 4, 24.05.2012, p. 691-705.

Research output: Contribution to journalArticle

Schafer, DP, Lehrman, EK, Kautzman, AG, Koyama, R, Mardinly, AR, Yamasaki, R, Ransohoff, RM, Greenberg, ME, Barres, BA & Stevens, B 2012, 'Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner', Neuron, vol. 74, no. 4, pp. 691-705. https://doi.org/10.1016/j.neuron.2012.03.026
Schafer, Dorothy P. ; Lehrman, Emily K. ; Kautzman, Amanda G. ; Koyama, Ryuta ; Mardinly, Alan R. ; Yamasaki, Ryo ; Ransohoff, Richard M. ; Greenberg, Michael E. ; Barres, Ben A. ; Stevens, Beth. / Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner. In: Neuron. 2012 ; Vol. 74, No. 4. pp. 691-705.
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