Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior

Nat Neurosci. 2014 Mar;17(3):400-6. doi: 10.1038/nn.3641. Epub 2014 Feb 2.


Microglia are phagocytic cells that infiltrate the brain during development and have a role in the elimination of synapses during brain maturation. Changes in microglial morphology and gene expression have been associated with neurodevelopmental disorders. However, it remains unknown whether these changes are a primary cause or a secondary consequence of neuronal deficits. Here we tested whether a primary deficit in microglia was sufficient to induce some autism-related behavioral and functional connectivity deficits. Mice lacking the chemokine receptor Cx3cr1 exhibit a transient reduction of microglia during the early postnatal period and a consequent deficit in synaptic pruning. We show that deficient synaptic pruning is associated with weak synaptic transmission, decreased functional brain connectivity, deficits in social interaction and increased repetitive-behavior phenotypes that have been previously associated with autism and other neurodevelopmental and neuropsychiatric disorders. These findings open the possibility that disruptions in microglia-mediated synaptic pruning could contribute to neurodevelopmental and neuropsychiatric disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Brain / metabolism
  • Brain / pathology*
  • CX3C Chemokine Receptor 1
  • Connectome / instrumentation
  • Connectome / methods*
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microglia / metabolism
  • Microglia / pathology*
  • Neurons / metabolism
  • Neurons / pathology*
  • Receptors, Chemokine / physiology
  • Signal Transduction / physiology*
  • Social Behavior*
  • Synapses / metabolism
  • Synaptic Transmission / physiology*


  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • Receptors, Chemokine