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

Christopher N Parkhurst1, Guang Yang2, Ipe Ninan3

  • 1Molecular Neurobiology Program, The Kimmel Center for Biology and Medicine at the Skirball Institute, Department of Neuroscience and Physiology, New York University School of Medicine, New York, NY 10016, USA.

Cell
|December 24, 2013
PubMed

Insights

Microglia, the brain's immune cells, are crucial for learning and memory. This study shows they promote synapse formation via brain-derived neurotrophic factor (BDNF), essential for cognitive function.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are CNS macrophages with known roles in pathology.
  • Their physiological functions in brain plasticity and cognition are not well understood.

Purpose of the Study:

  • To investigate the physiological roles of microglia in learning, memory, and synaptic plasticity.
  • To develop a method for specific microglial manipulation in the CNS.

Main Methods:

  • Generated CX3CR1(CreER) mice for inducible gene manipulation in microglia.
  • Depleted microglia using diphtheria toxin administration.
  • Assessed learning, memory, and synapse formation in depleted mice.
  • Examined the role of microglial brain-derived neurotrophic factor (BDNF) by genetic removal.

Main Results:

  • Microglia depletion impaired learning and motor-learning-dependent synapse formation.
  • Genetic removal of microglial BDNF mimicked the effects of microglia depletion.
  • Microglial BDNF enhances neuronal tropomyosin-related kinase receptor B phosphorylation, a key factor in synaptic plasticity.

Conclusions:

  • Microglia play essential physiological roles in learning and memory.
  • Microglia promote learning-related synapse formation through BDNF signaling.
  • Targeting microglial BDNF may offer therapeutic potential for cognitive disorders.

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