The role of microglia and their CX3CR1 signaling in adult neurogenesis in the olfactory bulb

Elife. 2017 Dec 18;6:e30809. doi: 10.7554/eLife.30809.

Abstract

Microglia play important roles in perinatal neuro- and synapto-genesis. To test the role of microglia in these processes during adulthood, we examined the effects of microglia depletion, via treatment of mice with the CSF-1 receptor antagonist PLX5622, and abrogated neuronal-microglial communication in CX3C receptor-1 deficient (Cx3cr1-/-) mice. Microglia depletion significantly lowered spine density in young (developing) but not mature adult-born-granule-cells (abGCs) in the olfactory bulb. Two-photon time-lapse imaging indicated that microglia depletion reduced spine formation and elimination. Functionally, odor-evoked responses of mitral cells, which are normally inhibited by abGCs, were increased in microglia-depleted mice. In Cx3cr1-/- mice, abGCs exhibited reduced spine density, dynamics and size, concomitantly with reduced contacts between Cx3cr1-deficient microglia and abGCs' dendritic shafts, along with increased proportion of microglia-contacted spines. Thus, during adult neurogenesis, microglia regulate the elimination (pruning), formation, and maintenance of synapses on newborn neurons, contributing to the functional integrity of the olfactory bulb circuitry.

Keywords: adult neruogenesis; development; microglia; mouse; neuroscience; olfactory bulb; spines; synapses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CX3C Chemokine Receptor 1 / genetics
  • CX3C Chemokine Receptor 1 / metabolism*
  • Cell Differentiation*
  • Mice
  • Mice, Knockout
  • Microglia / physiology*
  • Neurogenesis*
  • Olfactory Bulb / growth & development*
  • Signal Transduction*
  • Time-Lapse Imaging

Substances

  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.