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

Lookup NU author(s): Dr Rolando Berlinguer Palmini



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Berlinguer-Palmini R; Park H; Han KS; Seo J; Lee J; Dravid SM; Woo J; Chun H; Cho S; Bae JY; An H; Koh W; Yoon BE; Mannaioni G; Traynelis SF; Bae YC; Choi SY; Lee CJ

Publication type: Article

Publication status: Published

Journal: Molecular Brian

Year: 2015

Volume: 8

Online publication date: 03/02/2015

Acceptance date: 15/01/2015

Date deposited: 12/03/2015

ISSN (electronic): 1756-6606

Publisher: BioMed Central


DOI: 10.1186/s13041-015-0097-y


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Funder referenceFunder name
Ente Cassa di Risparmio di Firenze
Korea Institute of Science and Technology (KIST)
2E25210KIST institutional program
2014050477Korea Research Foundation (KRF)
NRF-2012M3C7A1055412Brain Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning