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

Mol Brain. 2015 Feb 3;8:7. doi: 10.1186/s13041-015-0097-y.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Bestrophins
  • CA1 Region, Hippocampal / metabolism
  • CA1 Region, Hippocampal / ultrastructure
  • Eye Proteins / metabolism*
  • Glutamic Acid / metabolism*
  • Hippocampus / metabolism*
  • Hippocampus / ultrastructure
  • Humans
  • Ion Channels / metabolism*
  • Long-Term Potentiation
  • Mice
  • Models, Biological
  • Neuronal Plasticity*
  • Receptor, PAR-1 / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Synapses / metabolism
  • Synaptic Transmission

Substances

  • Best1 protein, mouse
  • Bestrophins
  • Eye Proteins
  • Ion Channels
  • Receptor, PAR-1
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid