Synaptic pruning by microglia is necessary for normal brain development

Science. 2011 Sep 9;333(6048):1456-8. doi: 10.1126/science.1202529. Epub 2011 Jul 21.

Abstract

Microglia are highly motile phagocytic cells that infiltrate and take up residence in the developing brain, where they are thought to provide a surveillance and scavenging function. However, although microglia have been shown to engulf and clear damaged cellular debris after brain insult, it remains less clear what role microglia play in the uninjured brain. Here, we show that microglia actively engulf synaptic material and play a major role in synaptic pruning during postnatal development in mice. These findings link microglia surveillance to synaptic maturation and suggest that deficits in microglia function may contribute to synaptic abnormalities seen in some neurodevelopmental disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / growth & development*
  • Brain / physiology
  • CX3C Chemokine Receptor 1
  • Chemokine CX3CL1 / metabolism
  • Dendritic Spines / physiology
  • Dendritic Spines / ultrastructure
  • Disks Large Homolog 4 Protein
  • Excitatory Postsynaptic Potentials
  • Guanylate Kinases / analysis
  • Hippocampus / growth & development*
  • Hippocampus / physiology*
  • Long-Term Synaptic Depression
  • Membrane Proteins / analysis
  • Mice
  • Mice, Knockout
  • Microglia / physiology*
  • Miniature Postsynaptic Potentials
  • Neuronal Plasticity
  • Patch-Clamp Techniques
  • Pyramidal Cells / physiology
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism
  • Receptors, HIV / genetics
  • Receptors, HIV / metabolism
  • Signal Transduction
  • Synapses / physiology*
  • Synaptosomal-Associated Protein 25 / analysis

Substances

  • CX3C Chemokine Receptor 1
  • Chemokine CX3CL1
  • Cx3cl1 protein, mouse
  • Cx3cr1 protein, mouse
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Membrane Proteins
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Receptors, HIV
  • Snap25 protein, mouse
  • Synaptosomal-Associated Protein 25
  • Guanylate Kinases