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

Research output: Contribution to journalArticlepeer-review

48 Citations (Scopus)


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 languageEnglish
Article number7
JournalMolecular brain
Issue number1
Publication statusPublished - 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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