Cell
Volume 182, Issue 2, 23 July 2020, Pages 388-403.e15
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Article
Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity

https://doi.org/10.1016/j.cell.2020.05.050Get rights and content
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Highlights

  • IL-33 is expressed by subsets of hippocampal neurons and is modulated by experience

  • Microglia drive dendritic spine plasticity and memory precision via neuronal IL-33

  • IL-33 gain of function mitigates some age-related decreases in spine plasticity

  • Neuronal IL-33 induces microglial remodeling of the extracellular matrix

Summary

Synapse remodeling is essential to encode experiences into neuronal circuits. Here, we define a molecular interaction between neurons and microglia that drives experience-dependent synapse remodeling in the hippocampus. We find that the cytokine interleukin-33 (IL-33) is expressed by adult hippocampal neurons in an experience-dependent manner and defines a neuronal subset primed for synaptic plasticity. Loss of neuronal IL-33 or the microglial IL-33 receptor leads to impaired spine plasticity, reduced newborn neuron integration, and diminished precision of remote fear memories. Memory precision and neuronal IL-33 are decreased in aged mice, and IL-33 gain of function mitigates age-related decreases in spine plasticity. We find that neuronal IL-33 instructs microglial engulfment of the extracellular matrix (ECM) and that its loss leads to impaired ECM engulfment and a concomitant accumulation of ECM proteins in contact with synapses. These data define a cellular mechanism through which microglia regulate experience-dependent synapse remodeling and promote memory consolidation.

Keywords

microglia, hippocampus, extracellular matrix, aging, memory, dendrite remodeling, interleukin-33

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These authors contributed equally

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Twitter: @Phi_hD

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Twitter: @AnnaMolofskyLab

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