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

• Main Authors: Ronen Reshef, Elena Kudryavitskaya, Haran Shani-Narkiss, Batya Isaacson, Neta Rimmerman, Adi Mizrahi, Raz Yirmiya
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2017-12-01
• Series: eLife
• Subjects: adult neruogenesis; synapses; microglia; olfactory bulb; spines; development
• Online Access: https://elifesciences.org/articles/30809

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.