Channel-mediated astrocytic glutamate modulates hippocampal synaptic plasticity by activating postsynaptic NMDA receptors

Hyungju Park; Kyung Seok Han; Jinsoo Seo; Jaekwang Lee; Shashank M. Dravid; Junsung Woo; Heejung Chun; Sukhee Cho; Jin Young Bae; Heeyoung An; Woohyun Koh; Bo Eun Yoon; Rolando Berlinguer-Palmini; Guido Mannaioni; Stephen F. Traynelis; Yong Chul Bae; Se Young Choi; C. Justin Lee

doi:10.1186/s13041-015-0097-y

Channel-mediated astrocytic glutamate modulates hippocampal synaptic plasticity by activating postsynaptic NMDA receptors

Hyungju Park, Kyung Seok Han, Jinsoo Seo, Jaekwang Lee, Shashank M. Dravid, Junsung Woo, Heejung Chun, Sukhee Cho, Jin Young Bae, Heeyoung An, Woohyun Koh, Bo Eun Yoon, Rolando Berlinguer-Palmini, Guido Mannaioni, Stephen F. Traynelis, Yong Chul Bae, Se Young Choi, C. Justin Lee

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

45 Citations (Scopus)

Abstract

Background: Activation of G protein coupled receptor (GPCR) in astrocytes leads to Ca²⁺-dependent glutamate release via Bestrophin 1 (Best1) channel. Whether receptor-mediated glutamate release from astrocytes can regulate synaptic plasticity remains to be fully understood. Results: We show here that Best1-mediated astrocytic glutamate activates the synaptic N-methyl-D-aspartate receptor (NMDAR) and modulates NMDAR-dependent synaptic plasticity. Our data show that activation of the protease-activated receptor 1 (PAR1) in hippocampal CA1 astrocytes elevates the glutamate concentration at Schaffer collateral-CA1 (SC-CA1) synapses, resulting in activation of GluN2A-containing NMDARs and NMDAR-dependent potentiation of synaptic responses. Furthermore, the threshold for inducing NMDAR-dependent long-term potentiation (LTP) is lowered when astrocytic glutamate release accompanied LTP induction, suggesting that astrocytic glutamate is significant in modulating synaptic plasticity. Conclusions: Our results provide direct evidence for the physiological importance of channel-mediated astrocytic glutamate in modulating neural circuit functions.

Original language	English
Article number	7
Journal	Molecular brain
Volume	8
Issue number	1
DOIs	https://doi.org/10.1186/s13041-015-0097-y
Publication status	Published - 2015 Dec

Bibliographical note

Funding Information:
We thank Dr. T. Jacks for providing us with pSicoR lentiviral vector through Addgene Inc., Dr. R. Tsien for the pDisplay-GluSnFR vector, and Dr. K. McCarthy for hGFAP-CreERT2 transgenic mice. HP was supported by the Korea Institute of Science and Technology (KIST; Star-Postdoc. Fellowship). GM and RPL were supported by the Ente Cassa di Risparmio di Firenze. JS, S-HC, and S-Y C were supported by the Korea Research Foundation (KRF; grant 2014050477). SFT was supported by NIH (grant NS039419). CJL was supported by NIH (grant NS43875), KRF (grant KRF-2005-070-C00096), KIST institutional program (Project No. 2E25210), and Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2012M3C7A1055412).

Publisher Copyright:
© 2015 Park et al.; licensee BioMed Central.

All Science Journal Classification (ASJC) codes

Molecular Biology
Cellular and Molecular Neuroscience

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Park, H., Han, K. S., Seo, J., Lee, J., Dravid, S. M., Woo, J., Chun, H., Cho, S., Bae, J. Y., An, H., Koh, W., Yoon, B. E., Berlinguer-Palmini, R., Mannaioni, G., Traynelis, S. F., Bae, Y. C., Choi, S. Y., & Lee, C. J. (2015). Channel-mediated astrocytic glutamate modulates hippocampal synaptic plasticity by activating postsynaptic NMDA receptors. Molecular brain, 8(1), [7]. https://doi.org/10.1186/s13041-015-0097-y

Park, Hyungju ; Han, Kyung Seok ; Seo, Jinsoo ; Lee, Jaekwang ; Dravid, Shashank M. ; Woo, Junsung ; Chun, Heejung ; Cho, Sukhee ; Bae, Jin Young ; An, Heeyoung ; Koh, Woohyun ; Yoon, Bo Eun ; Berlinguer-Palmini, Rolando ; Mannaioni, Guido ; Traynelis, Stephen F. ; Bae, Yong Chul ; Choi, Se Young ; Lee, C. Justin. / Channel-mediated astrocytic glutamate modulates hippocampal synaptic plasticity by activating postsynaptic NMDA receptors. In: Molecular brain. 2015 ; Vol. 8, No. 1.

@article{a7daf3778bdb4d1dbd8fcaf1a6024d5b,

title = "Channel-mediated astrocytic glutamate modulates hippocampal synaptic plasticity by activating postsynaptic NMDA receptors",

abstract = "Background: Activation of G protein coupled receptor (GPCR) in astrocytes leads to Ca2+-dependent glutamate release via Bestrophin 1 (Best1) channel. Whether receptor-mediated glutamate release from astrocytes can regulate synaptic plasticity remains to be fully understood. Results: We show here that Best1-mediated astrocytic glutamate activates the synaptic N-methyl-D-aspartate receptor (NMDAR) and modulates NMDAR-dependent synaptic plasticity. Our data show that activation of the protease-activated receptor 1 (PAR1) in hippocampal CA1 astrocytes elevates the glutamate concentration at Schaffer collateral-CA1 (SC-CA1) synapses, resulting in activation of GluN2A-containing NMDARs and NMDAR-dependent potentiation of synaptic responses. Furthermore, the threshold for inducing NMDAR-dependent long-term potentiation (LTP) is lowered when astrocytic glutamate release accompanied LTP induction, suggesting that astrocytic glutamate is significant in modulating synaptic plasticity. Conclusions: Our results provide direct evidence for the physiological importance of channel-mediated astrocytic glutamate in modulating neural circuit functions.",

author = "Hyungju Park and Han, {Kyung Seok} and Jinsoo Seo and Jaekwang Lee and Dravid, {Shashank M.} and Junsung Woo and Heejung Chun and Sukhee Cho and Bae, {Jin Young} and Heeyoung An and Woohyun Koh and Yoon, {Bo Eun} and Rolando Berlinguer-Palmini and Guido Mannaioni and Traynelis, {Stephen F.} and Bae, {Yong Chul} and Choi, {Se Young} and Lee, {C. Justin}",

note = "Funding Information: We thank Dr. T. Jacks for providing us with pSicoR lentiviral vector through Addgene Inc., Dr. R. Tsien for the pDisplay-GluSnFR vector, and Dr. K. McCarthy for hGFAP-CreERT2 transgenic mice. HP was supported by the Korea Institute of Science and Technology (KIST; Star-Postdoc. Fellowship). GM and RPL were supported by the Ente Cassa di Risparmio di Firenze. JS, S-HC, and S-Y C were supported by the Korea Research Foundation (KRF; grant 2014050477). SFT was supported by NIH (grant NS039419). CJL was supported by NIH (grant NS43875), KRF (grant KRF-2005-070-C00096), KIST institutional program (Project No. 2E25210), and Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2012M3C7A1055412). Publisher Copyright: {\textcopyright} 2015 Park et al.; licensee BioMed Central.",

year = "2015",

month = dec,

doi = "10.1186/s13041-015-0097-y",

language = "English",

volume = "8",

journal = "Molecular Brain",

issn = "1756-6606",

publisher = "BioMed Central",

number = "1",

}

Park, H, Han, KS, Seo, J, Lee, J, Dravid, SM, Woo, J, Chun, H, Cho, S, Bae, JY, An, H, Koh, W, Yoon, BE, Berlinguer-Palmini, R, Mannaioni, G, Traynelis, SF, Bae, YC, Choi, SY & Lee, CJ 2015, 'Channel-mediated astrocytic glutamate modulates hippocampal synaptic plasticity by activating postsynaptic NMDA receptors', Molecular brain, vol. 8, no. 1, 7. https://doi.org/10.1186/s13041-015-0097-y

Channel-mediated astrocytic glutamate modulates hippocampal synaptic plasticity by activating postsynaptic NMDA receptors. / Park, Hyungju; Han, Kyung Seok; Seo, Jinsoo; Lee, Jaekwang; Dravid, Shashank M.; Woo, Junsung; Chun, Heejung; Cho, Sukhee; Bae, Jin Young; An, Heeyoung; Koh, Woohyun; Yoon, Bo Eun; Berlinguer-Palmini, Rolando; Mannaioni, Guido; Traynelis, Stephen F.; Bae, Yong Chul; Choi, Se Young; Lee, C. Justin.

In: Molecular brain, Vol. 8, No. 1, 7, 12.2015.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Channel-mediated astrocytic glutamate modulates hippocampal synaptic plasticity by activating postsynaptic NMDA receptors

AU - Park, Hyungju

AU - Han, Kyung Seok

AU - Seo, Jinsoo

AU - Lee, Jaekwang

AU - Dravid, Shashank M.

AU - Woo, Junsung

AU - Chun, Heejung

AU - Cho, Sukhee

AU - Bae, Jin Young

AU - An, Heeyoung

AU - Koh, Woohyun

AU - Yoon, Bo Eun

AU - Berlinguer-Palmini, Rolando

AU - Mannaioni, Guido

AU - Traynelis, Stephen F.

AU - Bae, Yong Chul

AU - Choi, Se Young

AU - Lee, C. Justin

N1 - Funding Information: We thank Dr. T. Jacks for providing us with pSicoR lentiviral vector through Addgene Inc., Dr. R. Tsien for the pDisplay-GluSnFR vector, and Dr. K. McCarthy for hGFAP-CreERT2 transgenic mice. HP was supported by the Korea Institute of Science and Technology (KIST; Star-Postdoc. Fellowship). GM and RPL were supported by the Ente Cassa di Risparmio di Firenze. JS, S-HC, and S-Y C were supported by the Korea Research Foundation (KRF; grant 2014050477). SFT was supported by NIH (grant NS039419). CJL was supported by NIH (grant NS43875), KRF (grant KRF-2005-070-C00096), KIST institutional program (Project No. 2E25210), and Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2012M3C7A1055412). Publisher Copyright: © 2015 Park et al.; licensee BioMed Central.

PY - 2015/12

Y1 - 2015/12

N2 - Background: Activation of G protein coupled receptor (GPCR) in astrocytes leads to Ca2+-dependent glutamate release via Bestrophin 1 (Best1) channel. Whether receptor-mediated glutamate release from astrocytes can regulate synaptic plasticity remains to be fully understood. Results: We show here that Best1-mediated astrocytic glutamate activates the synaptic N-methyl-D-aspartate receptor (NMDAR) and modulates NMDAR-dependent synaptic plasticity. Our data show that activation of the protease-activated receptor 1 (PAR1) in hippocampal CA1 astrocytes elevates the glutamate concentration at Schaffer collateral-CA1 (SC-CA1) synapses, resulting in activation of GluN2A-containing NMDARs and NMDAR-dependent potentiation of synaptic responses. Furthermore, the threshold for inducing NMDAR-dependent long-term potentiation (LTP) is lowered when astrocytic glutamate release accompanied LTP induction, suggesting that astrocytic glutamate is significant in modulating synaptic plasticity. Conclusions: Our results provide direct evidence for the physiological importance of channel-mediated astrocytic glutamate in modulating neural circuit functions.

AB - Background: Activation of G protein coupled receptor (GPCR) in astrocytes leads to Ca2+-dependent glutamate release via Bestrophin 1 (Best1) channel. Whether receptor-mediated glutamate release from astrocytes can regulate synaptic plasticity remains to be fully understood. Results: We show here that Best1-mediated astrocytic glutamate activates the synaptic N-methyl-D-aspartate receptor (NMDAR) and modulates NMDAR-dependent synaptic plasticity. Our data show that activation of the protease-activated receptor 1 (PAR1) in hippocampal CA1 astrocytes elevates the glutamate concentration at Schaffer collateral-CA1 (SC-CA1) synapses, resulting in activation of GluN2A-containing NMDARs and NMDAR-dependent potentiation of synaptic responses. Furthermore, the threshold for inducing NMDAR-dependent long-term potentiation (LTP) is lowered when astrocytic glutamate release accompanied LTP induction, suggesting that astrocytic glutamate is significant in modulating synaptic plasticity. Conclusions: Our results provide direct evidence for the physiological importance of channel-mediated astrocytic glutamate in modulating neural circuit functions.

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U2 - 10.1186/s13041-015-0097-y

DO - 10.1186/s13041-015-0097-y

M3 - Article

C2 - 25645137

AN - SCOPUS:84924190787

VL - 8

JO - Molecular Brain

JF - Molecular Brain

SN - 1756-6606

IS - 1

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ER -

Channel-mediated astrocytic glutamate modulates hippocampal synaptic plasticity by activating postsynaptic NMDA receptors

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