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Author Notes:

Correspondence: sychoi@snu.ac.kr; cjl@kist.re.kr

See publication for full list of author contributions.

All authors read and approved the final manuscript.

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.

The authors declare that they have no competing interests.

Subjects:

Research Funding:

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).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • Astrocytes
  • Bestrophin 1
  • Ca2+-activated anion channel
  • Synaptic plasticity
  • Glutamate
  • NMDA receptor
  • LTP
  • PAR1
  • TISSUE-PLASMINOGEN ACTIVATOR
  • LONG-TERM POTENTIATION
  • PYRAMIDAL NEURONS
  • ANION CHANNEL
  • TIME-COURSE
  • D-SERINE
  • IN-SITU
  • RELEASE
  • CALCIUM
  • CURRENTS

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

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Journal Title:

Molecular Brain

Volume:

Volume 8

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Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2015 Park et al.; licensee BioMed Central.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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