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

• Type of Material: Article
• Authors: Hyungju Park, Korea Institute of Science and Technology; Kyung-Seok Han, Korea Institute of Science and Technology; Jinsoo Seo, Seoul National University; Jaekwang Lee, Korea Institute of Science and Technology (KIST); Shashank M. Dravid, Creighton University; Junsung Woo, Korea Institute of Science and Technology (KIST); Heejung Chun, Korea Institute of Science and Technology (KIST); Sukhee Cho, Seoul National University; Jin Young Bae, Kyungpook National University; Heeyoung An, Korea Institute of Science and Technology; Woohyun Koh, Korea Institute of Science and Technology; Bo-Eun Yoon, Korea Institute of Science and Technology; Rolando Berlinguer-Palmini, Newcastle University; Guido Mannaioni, University of Florence; Stephen Traynelis, Emory University; Yong Chul Bae, Kyungpook National University; Se-Young Choi, Seoul National University; C. Justin Lee, Korea Institute of Science and Technology (KIST)
• Language: English
• Date: 2015-02-03
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Park et al.; licensee BioMed Central.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13041-015-0097-y
• Title of Journal or Parent Work: Molecular Brain
• ISSN: 1756-6606
• Volume: 8
• Grant/Funding Information: 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).; 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).; SFT was supported by NIH (grant NS039419).; HP was supported by the Korea Institute of Science and Technology (KIST; Star-Postdoc. Fellowship).
• Keywords: Neurosciences & Neurology; PYRAMIDAL NEURONS; NMDA receptor; Neurosciences; Ca2+-activated anion channel; Life Sciences & Biomedicine; Science & Technology; PAR1; RELEASE; Glutamate; TISSUE-PLASMINOGEN ACTIVATOR; IN-SITU; LTP; Astrocytes; CURRENTS; LONG-TERM POTENTIATION; Bestrophin 1; ANION CHANNEL; Synaptic plasticity; TIME-COURSE; D-SERINE; CALCIUM
• Research Categories: Health Sciences, Pharmacology; Biology, Neuroscience

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.