期刊
CELL
卷 155, 期 7, 页码 1596-1609出版社
CELL PRESS
DOI: 10.1016/j.cell.2013.11.030
关键词
-
资金
- NIH [R01 NS047325, P01 NS074972, RO1 MH96899, P41 GM103533, P01 AG031097, R01 MH067880, NS030687, F30 MH096370]
- McKnight Memory Disorder Award
- Whitehall Foundation
- Alzheimer's Association [NIRG-11-205362]
- National Institute of Aging Fellowship [F32 AG039127]
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 CX3CR1 CreER 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 thatmicroglia serve important physiological functions in learning and memory by promoting learning-related synapse formation through BDNF signaling.
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