The role of microglia and their CX3CR1 signaling in adult neurogenesis in the olfactory bulb.
Ronen ReshefElena KudryavitskayaHaran Shani-NarkissBatya IsaacsonNeta RimmermanAdi MizrahiRaz YirmiyaPublished in: eLife (2017)
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.
Keyphrases
- inflammatory response
- neuropathic pain
- spinal cord
- induced apoptosis
- spinal cord injury
- high fat diet induced
- lps induced
- lipopolysaccharide induced
- pregnant women
- mitral valve
- type diabetes
- heart failure
- high resolution
- mass spectrometry
- cell cycle arrest
- adipose tissue
- middle aged
- photodynamic therapy
- preterm birth
- aortic valve
- aortic stenosis