气候变化领域集成服务门户(CCPortal): Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus

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DOI	10.1073/pnas.2020810118
	Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus
	Wang Y.; Fu W.-Y.; Cheung K.; Hung K.-W.; Chen C.; Geng H.; Yung W.-H.; Qu J.Y.; Fu A.K.Y.; Ip N.Y.
发表日期	2021
ISSN	00278424
卷号	118 期号:1
英文摘要	Hippocampal synaptic plasticity is important for learning and memory formation. Homeostatic synaptic plasticity is a specific form of synaptic plasticity that is induced upon prolonged changes in neuronal activity to maintain network homeostasis. While astrocytes are important regulators of synaptic transmission and plasticity, it is largely unclear how they interact with neurons to regulate synaptic plasticity at the circuit level. Here, we show that neuronal activity blockade selectively increases the expression and secretion of IL-33 (interleukin-33) by astrocytes in the hippocampal cornu ammonis 1 (CA1) subregion. This IL-33 stimulates an increase in excitatory synapses and neurotransmission through the activation of neuronal IL-33 receptor complex and synaptic recruitment of the scaffold protein PSD-95. We found that acute administration of tetrodotoxin in hippocampal slices or inhibition of hippocampal CA1 excitatory neurons by optogenetic manipulation increases IL- 33 expression in CA1 astrocytes. Furthermore, IL-33 administration in vivo promotes the formation of functional excitatory synapses in hippocampal CA1 neurons, whereas conditional knockout of IL- 33 in CA1 astrocytes decreases the number of excitatory synapses therein. Importantly, blockade of IL-33 and its receptor signaling in vivo by intracerebroventricular administration of its decoy receptor inhibits homeostatic synaptic plasticity in CA1 pyramidal neurons and impairs spatial memory formation in mice. These results collectively reveal an important role of astrocytic IL-33 in mediating the negative-feedback signaling mechanism in homeostatic synaptic plasticity, providing insights into how astrocytes maintain hippocampal network homeostasis. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Hippocampal circuit; Homeostasis; Interleukin; Learning and memory; PSD-95
语种	英语
scopus关键词	disks large homolog 4; interleukin 33; interleukin 33 receptor; interleukin receptor; tetrodotoxin; unclassified drug; animal cell; animal experiment; animal tissue; Article; astrocyte; brain nerve cell; cell count; controlled study; cytokine release; hippocampal CA1 region; hippocampal slice; homeostasis; in vivo study; male; mental development; mouse; negative feedback; nerve cell network; nerve cell plasticity; neurotransmission; nonhuman; optogenetics; priority journal; protein expression; protein transport; pyramidal nerve cell; signal transduction; spatial memory; synaptogenesis
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181155
作者单位	Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, Hong Kong; Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, Hong Kong; State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, Hong Kong; Hong Kong Center for Neurodegenerative Diseases, Hong Kong; Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, Hong Kong; Center of Systems Biology and Human Health, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, Hong Kong; School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong; Gerald Choa Neuroscience Centre, The Chinese University of Hong Kong, Shatin, Hong Kong; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research ...
推荐引用方式 GB/T 7714	Wang Y.,Fu W.-Y.,Cheung K.,et al. Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus[J],2021,118(1).
APA	Wang Y..,Fu W.-Y..,Cheung K..,Hung K.-W..,Chen C..,...&Ip N.Y..(2021).Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus.Proceedings of the National Academy of Sciences of the United States of America,118(1).
MLA	Wang Y.,et al."Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus".Proceedings of the National Academy of Sciences of the United States of America 118.1(2021).