Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor

Christopher N. Parkhurst, Guang Yang, Ipe Ninan, Jeffrey N. Savas, John R. Yates, Juan J. Lafaille, Barbara L. Hempstead, Dan R. Littman, Wen Biao Gan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1816 Scopus citations


Microglia are the resident macrophages of the CNS, and their functions have been extensively studied in various brain pathologies. The physiological roles of microglia in brain plasticity and function, however, remain unclear. To address this question, we generated CX3CR1CreER mice expressing tamoxifen-inducible Cre recombinase that allow for specific manipulation of gene function in microglia. Using CX3CR1 CreER to drive diphtheria toxin receptor expression in microglia, we found that microglia could be specifically depleted from the brain upon diphtheria toxin administration. Mice depleted of microglia showed deficits in multiple learning tasks and a significant reduction in motor-learning-dependent synapse formation. Furthermore, Cre-dependent removal of brain-derived neurotrophic factor (BDNF) from microglia largely recapitulated the effects of microglia depletion. Microglial BDNF increases neuronal tropomyosin-related kinase receptor B phosphorylation, a key mediator of synaptic plasticity. Together, our findings reveal that microglia serve important physiological functions in learning and memory by promoting learning-related synapse formation through BDNF signaling.

Original languageEnglish (US)
Pages (from-to)1596-1609
Number of pages14
Issue number7
StatePublished - Dec 19 2013

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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