title: Astrocytes contribute to synapse elimination via type 2 inositol 1,4,5-trisphosphate receptor-dependent release of ATP.
abstract: 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 Ca(2+) 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.
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Lou
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Hao
authors.identifier: http://orcid.org/0000-0003-1862-8229
authors.initials: H
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D020651:Ventral Thalamic Nuclei / Q000502:physiology*
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; C546383:P2ry1 protein, mouse; D058472:Receptors, Purinergic P2Y1; D000255:Adenosine Triphosphate
keywords: ATP; astrocytes; mouse; neuroscience; purinergic signaling; synapse elimination