Astrocytic IP3Rs: Contribution to Ca2+ signalling and hippocampal LTP
Glia. 2017-01-07; 65(3): 502-513
DOI: 10.1002/glia.23107
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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).
Author information:
(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.
GLIA 2017;65:502-513.
© 2017 Wiley Periodicals, Inc.
DOI: 10.1002/glia.23107
PMID: 28063222 [Indexed for MEDLINE]