Sensory Experience Engages Microglia to Shape Neural Connectivity through a Non-Phagocytic Mechanism

Neuron. 2020 Nov 11;108(3):451-468.e9. doi: 10.1016/j.neuron.2020.08.002. Epub 2020 Sep 14.


Sensory experience remodels neural circuits in the early postnatal brain through mechanisms that remain to be elucidated. Applying a new method of ultrastructural analysis to the retinogeniculate circuit, we find that visual experience alters the number and structure of synapses between the retina and the thalamus. These changes require vision-dependent transcription of the receptor Fn14 in thalamic relay neurons and the induction of its ligand TWEAK in microglia. Fn14 functions to increase the number of bulbous spine-associated synapses at retinogeniculate connections, likely contributing to the strengthening of the circuit that occurs in response to visual experience. However, at retinogeniculate connections near TWEAK-expressing microglia, TWEAK signals via Fn14 to restrict the number of bulbous spines on relay neurons, leading to the elimination of a subset of connections. Thus, TWEAK and Fn14 represent an intercellular signaling axis through which microglia shape retinogeniculate connectivity in response to sensory experience.

Keywords: dendritic spine; development; microglia; pruning; sensory experience; synapse; synaptic refinement.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokine TWEAK / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microglia / physiology*
  • Microglia / ultrastructure*
  • Microscopy, Electron, Transmission / methods
  • Neuronal Plasticity / physiology*
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Photic Stimulation
  • Synapses / physiology*
  • Synapses / ultrastructure*
  • TWEAK Receptor / metabolism
  • Visual Pathways / physiology
  • Visual Pathways / ultrastructure


  • Cytokine TWEAK
  • TWEAK Receptor
  • Tnfrsf12a protein, mouse
  • Tnfsf12 protein, mouse