title: Astrocytic IP3Rs: Contribution to Ca2+signalling and hippocampal LTP.
abstract: Astrocytes regulate hippocampal synaptic plasticity by the Ca2+dependent release of the N-methyl d-aspartate receptor (NMDAR) co-agonist d-serine. Previous evidence indicated that d-serine release would be regulated by the intracellular Ca2+release channel IP3receptor (IP3R), however, genetic deletion of IP3R2, the putative astrocytic IP3R subtype, had no impact on synaptic plasticity or transmission. Although IP3R2 is widely believed to be the only functional IP3R in astrocytes, three IP3R subtypes (1, 2, and 3) have been identified in vertebrates. Therefore, to better understand gliotransmission, we investigated the functionality of IP3R and the contribution of the three IP3R subtypes to Ca2+signalling. As a proxy for gliotransmission, we found that long-term potentiation (LTP) was impaired by dialyzing astrocytes with the broad IP3R blocker heparin, and rescued by exogenous d-serine, indicating that astrocytic IP3Rs regulate d-serine release. To explore which IP3R subtypes are functional in astrocytes, we used pharmacology and two-photon Ca2+imaging of hippocampal slices from transgenic mice (IP3R2-/-and IP3R2-/-;3-/-). This approach revealed that underneath IP3R2-mediated global Ca2+events are an overlooked class of IP3R-mediated local events, occurring in astroglial processes. Notably, multiple IP3Rs were recruited by high frequency stimulation of the Schaffer collaterals, a classical LTP induction protocol. Together, these findings show the dependence of LTP and gliotransmission on Ca2+release by astrocytic IP3Rs. GLIA 2017;65:502-513.
authors.affiliation: INSERM U1215, Neurocentre Magendie, Bordeaux, 33077, France.|Université de Bordeaux, Bordeaux, 33077, France.|Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
authors.forename: Mark William
authors.identifier: 0000-0002-3780-6329
authors.initials: MW
authors.lastname: Sherwood
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
authors.forename: Misa
authors.initials: M
authors.lastname: Arizono
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Hisatsune
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.|Division of Biological Sciences, Graduate School of Science, Nagoya University, Furo-cho, Chikusa, Nagoya, 464-8602, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Bannai
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Ebisui
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02138, USA.
authors.forename: John Lawrence
authors.initials: JL
authors.lastname: Sherwood
authors.affiliation: INSERM U1215, Neurocentre Magendie, Bordeaux, 33077, France.|Université de Bordeaux, Bordeaux, 33077, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Panatier
authors.affiliation: INSERM U1215, Neurocentre Magendie, Bordeaux, 33077, France.|Université de Bordeaux, Bordeaux, 33077, France.
authors.forename: Stéphane Henri Richard
authors.initials: SH
authors.lastname: Oliet
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D014162:Transfection
chemical_list: D002135:Calcium-Binding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008164:Luminescent Proteins; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol
keywords: calcium; d-serine; glia; gliotransmission; plasticity; synapse