@article{393b2672e07f4bcca2e200ed0e94afdd,
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 (US)",
volume = "8",
journal = "Molecular Brain",
issn = "1756-6606",
publisher = "BioMed Central",
number = "1",
}