Astrocytic IP3Rs: Contribution to Ca2+ signalling and hippocampal LTP
Glia. 2017-01-07; 65(3): 502-513
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1. Glia. 2017 Mar;65(3):502-513. doi: 10.1002/glia.23107. Epub 2017 Jan 7.
Astrocytic IP3 Rs: Contribution to Ca2+ signalling and hippocampal LTP.
Sherwood MW(1)(2)(3), Arizono M(3), Hisatsune C(3), Bannai H(3)(4), Ebisui E(3),
Sherwood JL(5), Panatier A(1)(2), Oliet SH(1)(2), Mikoshiba K(3).
(1)INSERM U1215, Neurocentre Magendie, Bordeaux, 33077, France.
(2)Université de Bordeaux, Bordeaux, 33077, France.
(3)Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, 2-1
Hirosawa, Wako, Saitama, 351-0198, Japan.
(4)Division of Biological Sciences, Graduate School of Science, Nagoya
University, Furo-cho, Chikusa, Nagoya, 464-8602, Japan.
(5)Department of Stem Cell and Regenerative Biology, Harvard University,
Cambridge, MA, 02138, USA.
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 IP3 receptor (IP3 R), however, genetic deletion of IP3 R2,
the putative astrocytic IP3 R subtype, had no impact on synaptic plasticity or
transmission. Although IP3 R2 is widely believed to be the only functional IP3 R
in astrocytes, three IP3 R subtypes (1, 2, and 3) have been identified in
vertebrates. Therefore, to better understand gliotransmission, we investigated
the functionality of IP3 R and the contribution of the three IP3 R subtypes to
Ca2+ signalling. As a proxy for gliotransmission, we found that long-term
potentiation (LTP) was impaired by dialyzing astrocytes with the broad IP3 R
blocker heparin, and rescued by exogenous d-serine, indicating that astrocytic
IP3 Rs regulate d-serine release. To explore which IP3 R subtypes are functional
in astrocytes, we used pharmacology and two-photon Ca2+ imaging of hippocampal
slices from transgenic mice (IP3 R2-/- and IP3 R2-/- ;3-/- ). This approach
revealed that underneath IP3 R2-mediated global Ca2+ events are an overlooked
class of IP3 R-mediated local events, occurring in astroglial processes. Notably,
multiple IP3 Rs 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 IP3 Rs.
© 2017 Wiley Periodicals, Inc.
PMID: 28063222 [Indexed for MEDLINE]