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Interaction between Ephrins and mGlu5 Metabotropic Glutamate Receptors in the Induction of Long-Term Synaptic Depression in the Hippocampus
- Source :
- The Journal of Neuroscience. 30:2835-2843
- Publication Year :
- 2010
- Publisher :
- Society for Neuroscience, 2010.
-
Abstract
- We applied the group-I metabotropic glutamate (mGlu) receptor agonist, 3,5-dihydroxyphenylglycine (DHPG), to neonatal or adult rat hippocampal slices at concentrations (10 μm) that induced a short-term depression (STD) of excitatory synaptic transmission at the Schaffer collateral/CA1 synapses. DHPG-induced STD was entirely mediated by the activation of mGlu5 receptors because it was abrogated by the mGlu5 receptor antagonist, MPEP [2-methyl-6-(phenylethynyl)pyridine], but not by the mGlu1 receptor antagonist, CPCCOEt [7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester]. Knowing that ephrin-Bs functionally interact with group-I mGlu receptors (Calò et al., 2005), we examined whether pharmacological activation of ephrin-Bs could affect DHPG-induced STD. We activated ephrin-Bs using their cognate receptor, EphB1, under the form of a preclustered EphB1/Fc chimera. Addition of clustered EphB1/Fc alone to the slices induced a small but nondecremental depression of excitatory synaptic transmission, which differed from the depression induced by 10 μmDHPG. Surprisingly, EphB1/Fc-induced synaptic depression was abolished by MPEP (but not by CPCCOEt) suggesting that it required the endogenous activation of mGlu5 receptors. In addition, coapplication of DHPG and EphB1/Fc, resulted in a large and nondecremental long-term depression. The effect of clustered EphB1/Fc was specific because it was not mimicked by unclustered EphB1/Fc or clustered EphA1/Fc. These findings raise the intriguing possibility that changes in synaptic efficacy mediated by mGlu5 receptors are under the control of the ephrin/Eph receptor system, and that the neuronal actions of ephrins can be targeted by drugs that attenuate mGlu5 receptor signaling.
- Subjects :
- area ca1
Male
Patch-Clamp Techniques
Receptor, EphB1
Pyridines
mouse model
rat hippocampus
Receptor, Metabotropic Glutamate 5
Recombinant Fusion Proteins
Glutamic Acid
Ephrin-B1
in-vitro
Receptors, Metabotropic Glutamate
Hippocampus
Synaptic Transmission
glutamate-receptor-5 mglur5
Organ Culture Techniques
ca1 region
Excitatory Amino Acid Agonists
medicine
Animals
eph receptors
Rats, Wistar
Long-term depression
dhpg-induced ltd
Long-Term Synaptic Depression
Chemistry
General Neuroscience
Metabotropic glutamate receptor 7
Excitatory Postsynaptic Potentials
protein-synthesis
Articles
x mental-retardation
Rats
Metabotropic receptor
Synaptic fatigue
medicine.anatomical_structure
Schaffer collateral
Metabotropic glutamate receptor
Metabotropic glutamate receptor 1
Ephrins
Excitatory Amino Acid Antagonists
Neuroscience
Subjects
Details
- ISSN :
- 15292401 and 02706474
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- The Journal of Neuroscience
- Accession number :
- edsair.doi.dedup.....d07b7fd8ac7a4757fff3e1db671db71b