Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2020 Jul 3

PMID 32615087

Citations 251

Authors

Phi T Nguyen

Leah C Dorman

Simon Pan

Ilia D Vainchtein

Rafael T Han

Hiromi Nakao-Inoue

Sunrae E Taloma

Jerika J Barron

Ari B Molofsky

Mazen A Kheirbek

Anna V Molofsky

Affiliations

Soon will be listed here.

Abstract

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.

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