Microglia mediate forgetting via complement-dependent synaptic elimination

被引：412

作者：

Wang, Chao ^{[1
,2
,3
]}

Yue, Huimin ^{[1
,2
,3
]}

Hu, Zhechun ^{[1
,2
,3
]}

Shen, Yuwen ^{[1
,2
,3
]}

Ma, Jiao ^{[4
]}

Li, Jie ^{[1
,2
,3
]}

Wang, Xiao-Dong ^{[5
,6
]}

Wang, Liang ^{[7
,8
]}

Sun, Binggui ^{[9
,10
]}

Shi, Peng ^{[11
]}

Wang, Lang ^{[4
]}

Gu, Yan ^{[1
,2
,3
,12
]}

机构：

[1] Zhejiang Univ, Sch Med, NHC & CAMS Key Lab Med Neurobiol, Affiliated Hosp 2,Inst Neurosci, Hangzhou 310058, Peoples R China

[2] Zhejiang Univ, Sch Med, NHC & CAMS Key Lab Med Neurobiol, Affiliated Hosp 2,Dept Neurol, Hangzhou 310058, Peoples R China

[3] Zhejiang Univ, Sch Med, Ctr Stem Cell & Regenerat Med, Hangzhou 310058, Peoples R China

[4] Zhejiang Univ, Sch Med, Interdisciplinary Inst Neurosci & Technol, Dept Neurol,Affiliated Hosp 1, Hangzhou 310029, Peoples R China

[5] Zhejiang Univ, Sch Med, NHC & CAMS Key Lab Med Neurobiol, Dept Neurobiol,Inst Neurosci, Hangzhou 310058, Peoples R China

[6] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Psychiat, Hangzhou 310016, Peoples R China

[7] Zhejiang Univ, Sch Med, NHC & CAMS Key Lab Med Neurobiol, Mental Hlth Ctr,Affiliated Hosp 2,Inst Neurosci, Hangzhou 310058, Peoples R China

[8] Zhejiang Univ, Sch Med, NHC & CAMS Key Lab Med Neurobiol, Mental Hlth Ctr,Affiliated Hosp 2,Dept Neurol, Hangzhou 310058, Peoples R China

[9] Zhejiang Univ, Sch Med, NHC & CAMS Key Lab Med Neurobiol, Affiliated Hosp 1,Ctr Neurosci, Hangzhou 310058, Peoples R China

[10] Zhejiang Univ, Sch Med, NHC & CAMS Key Lab Med Neurobiol, Affiliated Hosp 1,Dept Neurol, Hangzhou 310058, Peoples R China

[11] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Cardiol, Hangzhou 310058, Peoples R China

[12] Zhejiang Prov Key Lab Tissue Engn & Regenerat Med, Hangzhou 310058, Peoples R China

来源：

SCIENCE | 2020年 / 367卷 / 6478期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

SYNAPSES IN-VIVO; HIPPOCAMPAL NEUROGENESIS; NEURONS BORN; PLASTICITY; CNS; ROLES;

D O I：

10.1126/science.aaz2288

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Synapses between engram cells are believed to be substrates for memory storage, and the weakening or loss of these synapses leads to the forgetting of related memories. We found engulfment of synaptic components by microglia in the hippocampi of healthy adult mice. Depletion of microglia or inhibition of microglial phagocytosis prevented forgetting and the dissociation of engram cells. By introducing CD55 to inhibit complement pathways, specifically in engram cells, we further demonstrated that microglia regulated forgetting in a complement- and activity-dependent manner. Additionally, microglia were involved in both neurogenesis-related and neurogenesis-unrelated memory degradation. Together, our findings revealed complement-dependent synapse elimination by microglia as a mechanism underlying the forgetting of remote memories.

引用

页码：688 / +

页数：25

共 35 条

[1] Hippocampal Neurogenesis Regulates Forgetting During Adulthood and Infancy [J].

Akers, Katherine G. ;

Martinez-Canabal, Alonso ;

Restivo, Leonardo ;

Yiu, Adelaide P. ;

De Cristofaro, Antonietta ;

Hsiang, Hwa-Lin ;

Wheeler, Anne L. ;

Guskjolen, Axel ;

Niibori, Yosuke ;

Shoji, Hirotaka ;

Ohira, Koji ;

Richards, Blake A. ;

Miyakawa, Tsuyoshi ;

Josselyn, Sheena A. ;

Frankland, Paul W. .

SCIENCE, 2014, 344 (6184) :598-602

[2]

[Anonymous], 2016, Cold Spring Harb. Perspect. Biol, DOI DOI 10.1101/CSHPERSPECT.A018903

[3] Impermanence of dendritic spines in live adult CA1 hippocampus [J].

Attardo, Alessio ;

Fitzgerald, James E. ;

Schnitzer, Mark J. .

NATURE, 2015, 523 (7562) :592-+

[4] Rapid Structural Remodeling of Thalamocortical Synapses Parallels Experience-Dependent Functional Plasticity in Mouse Primary Visual Cortex [J].

Coleman, Jason E. ;

Nahmani, Marc ;

Gavornik, Jeffrey P. ;

Haslinger, Robert ;

Heynen, Arnold J. ;

Erisir, Alev ;

Bear, Mark F. .

JOURNAL OF NEUROSCIENCE, 2010, 30 (29) :9670-9682

[5] Hippocampal neurogenesis and forgetting [J].

Frankland, Paul W. ;

Koehler, Stefan ;

Josselyn, Sheena A. .

TRENDS IN NEUROSCIENCES, 2013, 36 (09) :497-503

[6] Experience-dependent structural plasticity in the cortex [J].

Fu, Min ;

Zuo, Yi .

TRENDS IN NEUROSCIENCES, 2011, 34 (04) :177-187

[7] Optical controlling reveals time-dependent roles for adult-born dentate granule cells [J].

Gu, Yan ;

Arruda-Carvalho, Maithe ;

Wang, Jia ;

Janoschka, Stephen R. ;

Josselyn, Sheena A. ;

Frankland, Paul W. ;

Ge, Shaoyu .

NATURE NEUROSCIENCE, 2012, 15 (12) :1700-+

[8] Permanent Genetic Access to Transiently Active Neurons via TRAP: Targeted Recombination in Active Populations [J].

Guenthner, Casey J. ;

Miyamichi, Kazunari ;

Yang, Helen H. ;

Heller, H. Craig ;

Luo, Liqun .

NEURON, 2013, 78 (05) :773-784

[9]

Han JH, 2007, SCIENCE, V316, P457, DOI [10.1126/science.1139438, 10.1126/science.1134697]

[10] Experience leaves a lasting structural trace in cortical circuits [J].

Hofer, Sonja B. ;

Mrsic-Flogel, Thomas D. ;

Bonhoeffer, Tobias ;

Huebener, Mark .

NATURE, 2009, 457 (7227) :313-U4

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