TY - JOUR
T1 - Astrocytic IP3Rs
T2 - Contribution to Ca2+ signalling and hippocampal LTP
AU - Sherwood, Mark William
AU - Arizono, Misa
AU - Hisatsune, Chihiro
AU - Bannai, Hiroko
AU - Ebisui, Etsuko
AU - Sherwood, John Lawrence
AU - Panatier, Aude
AU - Oliet, Stéphane Henri Richard
AU - Mikoshiba, Katsuhiko
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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 (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.
AB - 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 (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.
KW - calcium
KW - d-serine
KW - glia
KW - gliotransmission
KW - plasticity
KW - synapse
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U2 - 10.1002/glia.23107
DO - 10.1002/glia.23107
M3 - Article
C2 - 28063222
AN - SCOPUS:85008430254
VL - 65
SP - 502
EP - 513
JO - GLIA
JF - GLIA
SN - 0894-1491
IS - 3
ER -