Park, Hyungju Han, Kyung-Seok Seo, Jinsoo Lee, Jaekwang Dravid, Shashank M. Woo, Junsung Chun, Heejung Cho, Sukhee Bae, Jin Young An, Heeyoung Koh, Woohyun Yoon, Bo-Eun Berlinguer-Palmini, Rolando Mannaioni, Guido Traynelis, Stephen F. Bae, Yong Chul Choi, Se-Young Lee, C. Justin 2024-01-20T07:34:29Z 2024-01-20T07:34:29Z 2021-09-05 2015-02-03 1756-6606 https://pubs.kist.re.kr/handle/201004/125776 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. English BIOMED CENTRAL LTD 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 Article 10.1186/s13041-015-0097-y 1 MOLECULAR BRAIN, v.8 MOLECULAR BRAIN 8 scie scopus 000349119700001 2-s2.0-84924190787 Neurosciences Neurosciences & Neurology Article TISSUE-PLASMINOGEN ACTIVATOR LONG-TERM POTENTIATION PYRAMIDAL NEURONS ANION CHANNEL TIME-COURSE D-SERINE IN-SITU RELEASE CALCIUM CURRENTS Astrocytes Bestrophin 1 Ca2+-activated anion channel Synaptic plasticity Glutamate NMDA receptor LTP PAR1