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Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity.
Cell ( IF 45.5 ) Pub Date : 2020-07-01 , DOI: 10.1016/j.cell.2020.05.050
Phi T Nguyen 1 , Leah C Dorman 2 , Simon Pan 2 , Ilia D Vainchtein 3 , Rafael T Han 3 , Hiromi Nakao-Inoue 3 , Sunrae E Taloma 3 , Jerika J Barron 1 , Ari B Molofsky 4 , Mazen A Kheirbek 5 , Anna V Molofsky 5
Affiliation  

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.



中文翻译:

小胶质细胞外基质的重塑促进突触可塑性。

突触重塑对于将经验编码到神经元回路中至关重要。在这里,我们定义了神经元和小胶质细胞之间的分子相互作用,该相互作用驱动了海马中依赖经验的突触重塑。我们发现细胞因子白介素33(IL-33)由成年海马神经元以经验依赖的方式表达,并定义了引发突触可塑性的神经元子集。神经元IL-33或小胶质细胞IL-33受体的丧失会导致脊柱可塑性受损,新生儿神经元整合减少以及远程恐惧记忆的准确性降低。衰老小鼠的记忆精确度和神经元IL-33降低,IL-33功能的获得减轻了与年龄相关的脊柱可塑性下降。我们发现,神经元IL-33指示细胞外基质(ECM)的小胶质细胞吞噬,并且其损失导致受损的ECM吞噬和伴随突触的ECM蛋白伴随积累。这些数据定义了一种细胞机制,小胶质细胞通过该机制调节经验依赖的突触重塑并促进记忆巩固。

更新日期:2020-07-23
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