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 Ca(2+)-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.
authors: Hyungju
authors: H
authors: Park
authors: Kyung-Seok
authors: KS
authors: Han
authors: Jinsoo
authors: J
authors: Seo
authors: Jaekwang
authors: J
authors: Lee
authors: Shashank M
authors: SM
authors: Dravid
authors: Junsung
authors: J
authors: Woo
authors: Heejung
authors: H
authors: Chun
authors: Sukhee
authors: S
authors: Cho
authors: Jin Young
authors: JY
authors: Bae
authors: Heeyoung
authors: H
authors: An
authors: Woohyun
authors: W
authors: Koh
authors: Bo-Eun
authors: BE
authors: Yoon
authors: Rolando
authors: R
authors: Berlinguer-Palmini
authors: Guido
authors: G
authors: Mannaioni
authors: Stephen F
authors: SF
authors: Traynelis
authors: Yong Chul
authors: YC
authors: Bae
authors: Se-Young
authors: SY
authors: Choi
authors: C Justin
authors: CJ
authors: Lee
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D000075002:Bestrophins; D056547:CA1 Region, Hippocampal / Q000378:metabolism / Q000648:ultrastructure; D005136:Eye Proteins / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D017774:Long-Term Potentiation; D051379:Mice; D008954:Models, Biological; D009473:Neuronal Plasticity; D044463:Receptor, PAR-1 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: C491856:Best1 protein, mouse; D000075002:Bestrophins; D005136:Eye Proteins; D007473:Ion Channels; D044463:Receptor, PAR-1; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid
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