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Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity.
Cell. 2020 Jul 23; 182(2):388-403.e15.Cell

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.

Authors+Show Affiliations

Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA.Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA.Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA.Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA.Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, USA.Department of Psychiatry and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, USA. Electronic address: anna.molofsky@ucsf.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32615087

Citation

Nguyen, Phi T., et al. "Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity." Cell, vol. 182, no. 2, 2020, pp. 388-403.e15.
Nguyen PT, Dorman LC, Pan S, et al. Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity. Cell. 2020;182(2):388-403.e15.
Nguyen, P. T., Dorman, L. C., Pan, S., Vainchtein, I. D., Han, R. T., Nakao-Inoue, H., Taloma, S. E., Barron, J. J., Molofsky, A. B., Kheirbek, M. A., & Molofsky, A. V. (2020). Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity. Cell, 182(2), 388-e15. https://doi.org/10.1016/j.cell.2020.05.050
Nguyen PT, et al. Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity. Cell. 2020 Jul 23;182(2):388-403.e15. PubMed PMID: 32615087.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity. AU - Nguyen,Phi T, AU - Dorman,Leah C, AU - Pan,Simon, AU - Vainchtein,Ilia D, AU - Han,Rafael T, AU - Nakao-Inoue,Hiromi, AU - Taloma,Sunrae E, AU - Barron,Jerika J, AU - Molofsky,Ari B, AU - Kheirbek,Mazen A, AU - Molofsky,Anna V, Y1 - 2020/07/01/ PY - 2019/12/29/received PY - 2020/04/20/revised PY - 2020/05/27/accepted PY - 2020/7/3/pubmed PY - 2020/7/3/medline PY - 2020/7/3/entrez KW - microglia, hippocampus, extracellular matrix, aging, memory, dendrite remodeling, interleukin-33 SP - 388 EP - 403.e15 JF - Cell JO - Cell VL - 182 IS - 2 N2 - 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. SN - 1097-4172 UR - https://www.unboundmedicine.com/medline/citation/32615087/Microglial_Remodeling_of_the_Extracellular_Matrix_Promotes_Synapse_Plasticity L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(20)30683-8 DB - PRIME DP - Unbound Medicine ER -
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