Astrocytes contribute to synapse elimination via type 2 inositol 1,4,5-trisphosphate receptor-dependent release of ATP

被引：58

作者：

Yang, Junhua ^{[1
]}

Yang, Hongbin ^{[1
]}

Liu, Yali ^{[1
]}

Li, Xia ^{[1
]}

Qin, Liming ^{[1
]}

Lou, Huifang ^{[1
]}

Duan, Shumin ^{[1
]}

Wang, Hao ^{[1
]}

机构：

[1] Zhejiang Univ, Key Lab Med Neurobiol, Dept Neurobiol, Minist Hlth China,Key Lab Neurobiol,Sch Med, Hangzhou, Zhejiang, Peoples R China

来源：

ELIFE | 2016年 / 5卷

基金：

中国国家自然科学基金;

关键词：

LONG-TERM POTENTIATION; CELLULAR EXPRESSION; IN-SITU; CA1; PLASTICITY; THALAMUS; GLIA; REFINEMENT; MICROGLIA; TRIGGERS;

D O I：

10.7554/eLife.15043

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Selective elimination of unwanted synapses is vital for the precise formation of neuronal circuits during development, but the underlying mechanisms remain unclear. Using inositol 1,4,5-trisphosphate receptor type 2 knockout (Itpr2(-/-)) mice to specifically disturb somatic Ca2+ signaling in astrocytes, we showed that developmental elimination of the ventral posteromedial nucleus relay synapse was impaired. Interestingly, intracerebroventricular injection of ATP, but not adenosine, rescued the deficit in synapse elimination in Itpr2(-/)-mice. Further studies showed that developmental synapse elimination was also impaired in P2ry1(-/)-mice and was not rescued by ATP, indicating a possible role of purinergic signaling. This hypothesis was confirmed by MRS-2365, a selective P2Y1 agonist, could also rescue the deficient of synapse elimination in Itpr2(-/)-mice. Our results uncovered a novel mechanism suggesting that astrocytes release ATP in an IP3R2-dependent manner to regulate synapse elimination.

引用

页数：17

共 49 条

[1] Hippocampal Short- and Long-Term Plasticity Are Not Modulated by Astrocyte Ca2+ Signaling [J].

Agulhon, Cendra ;

Fiacco, Todd A. ;

McCarthy, Ken D. .

SCIENCE, 2010, 327 (5970) :1250-1254

[2] Astrocyte Regulation of Synaptic Behavior [J].

Allen, Nicola J. .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 30, 2014, 30 :439-463

[3] Tripartite synapses: glia, the unacknowledged partner [J].

Araque, A ;

Parpura, V ;

Sanzgiri, RP ;

Haydon, PG .

TRENDS IN NEUROSCIENCES, 1999, 22 (05) :208-215

[4] Gliotransmitters Travel in Time and Space [J].

Araque, Alfonso ;

Carmignoto, Giorgio ;

Haydon, Philip G. ;

Oliet, Stephane H. R. ;

Robitaille, Richard ;

Volterra, Andrea .

NEURON, 2014, 81 (04) :728-739

[5] Developmental remodelling of the lemniscal synapse in the ventral basal thalamus of the mouse [J].

Arsenault, Dany ;

Zhang, Zhong-wei .

JOURNAL OF PHYSIOLOGY-LONDON, 2006, 573 (01) :121-132

[6] Synapse elimination accompanies functional plasticity in hippocampal neurons [J].

Bastrikova, Natalia ;

Gardner, Gregory A. ;

Reece, Jeff M. ;

Jeromin, Andreas ;

Dudek, Serena M. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (08) :3123-3127

[7] RETRACTED: TGF-β signaling regulates neuronal Clq expression and developmental synaptic refinement (Retracted Article) [J].

Bialas, Allison R. ;

Stevens, Beth .

NATURE NEUROSCIENCE, 2013, 16 (12) :1773-1782

[8] Astrocyte-derived ATP modulates depressive-like behaviors [J].

Cao, Xiong ;

Li, Liang-Ping ;

Wang, Qian ;

Wu, Qiong ;

Hu, Hong-Hai ;

Zhang, Meng ;

Fang, Ying-Ying ;

Zhang, Jie ;

Li, Shu-Ji ;

Xiong, Wen-Chao ;

Yan, Hua-Cheng ;

Gao, Yu-Bo ;

Liu, Ji-Hong ;

Li, Xiao-Wen ;

Sun, Li-Rong ;

Zeng, Yuan-Ning ;

Zhu, Xin-Hong ;

Gao, Tian-Ming .

NATURE MEDICINE, 2013, 19 (06) :773-+

[9] Developmental remodeling of the retinogeniculate synapse [J].

Chen, CF ;

Regehr, WG .

NEURON, 2000, 28 (03) :955-966

[10] Heterosynaptic long-term depression mediated by ATP released from astrocytes [J].

Chen, Jiadong ;

Tan, Zhibing ;

Zeng, Li ;

Zhang, Xiaoxing ;

He, You ;

Gao, Wei ;

Wu, Xiumei ;

Li, Yuju ;

Bu, Bitao ;

Wang, Wei ;

Duan, Shumin .

GLIA, 2013, 61 (02) :178-191

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