Neuron-glia communication via EphA4/ephrin-A3 modulates LTP through glial glutamate transport.
Journal:
Nat. Neurosci. 2009 OctAuthors:
Filosa A, Paixão S, Honsek SD, Carmona MA, Becker L, Feddersen B, Gaitanos L, Rudhard Y, Schoepfer R, Klopstock T, Kullander K, Rose CR, Pasquale EB, Klein R
Abstract
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 astro
...[more]cytes. 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.[less]
Mesh Headings:
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