期刊
CELL
卷 182, 期 2, 页码 388-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2020.05.050
关键词
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资金
- Pew Charitable Trusts
- NIMH [R01 MH108623, R01 MH111754, R01 MH117961, R01MH119349, DP2MH116507]
- Brain and Behavior Research Foundation
- Burroughs Wellcome Fund
- National Science Foundation [1650113]
- One Mind Rising Star Award
- Human Frontier Science Program
- Esther A. and Joseph Klingenstein Fund
- McKnight Memory and Cognitive Disorders Award
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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