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Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport.

Nature neuroscience | Oct 28, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19734893

Astrocytes are critical participants in synapse development and function, but their role in synaptic plasticity is unclear. Eph receptors and their ephrin ligands have been suggested to regulate neuron-glia interactions, and EphA4-mediated ephrin reverse signaling is required for synaptic plasticity in the hippocampus. Here we show that long-term potentiation (LTP) at the CA3-CA1 synapse is modulated by EphA4 in the postsynaptic CA1 cell and by ephrin-A3, a ligand of EphA4 that is found in astrocytes. Lack of EphA4 increased the abundance of glial glutamate transporters, and ephrin-A3 modulated transporter currents in astrocytes. Pharmacological inhibition of glial glutamate transporters rescued the LTP defects in EphA4 (Epha4) and ephrin-A3 (Efna3) mutant mice. Transgenic overexpression of ephrin-A3 in astrocytes reduces glutamate transporter levels and produces focal dendritic swellings possibly caused by glutamate excitotoxicity. These results suggest that EphA4/ephrin-A3 signaling is a critical mechanism for astrocytes to regulate synaptic function and plasticity.

Pubmed ID: 19734893 RIS Download

Mesh terms: Animals | Animals, Newborn | Aspartic Acid | Biophysics | Disease Models, Animal | Electric Stimulation | Ephrin-A3 | Excitatory Amino Acid Antagonists | Excitatory Amino Acid Transporter 1 | Excitatory Postsynaptic Potentials | Glial Fibrillary Acidic Protein | Glutamic Acid | Green Fluorescent Proteins | Hippocampus | Long-Term Potentiation | Mice | Mice, Inbred C57BL | Mice, Transgenic | Neuroglia | Neurons | Organ Culture Techniques | Patch-Clamp Techniques | Pentylenetetrazole | Receptor, EphA4 | Seizures | Signal Transduction | Synapses | Up-Regulation

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Associated grants

  • Agency: NICHD NIH HHS, Id: HD025938
  • Agency: NICHD NIH HHS, Id: P01 HD025938
  • Agency: Biotechnology and Biological Sciences Research Council, Id:
  • Agency: Wellcome Trust, Id:

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