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Interaction between ephrins and mGlu5 metabotropic glutamate receptors in the induction of long-term synaptic depression in the hippocampus


Reference:

Piccinin, S., Cinque, C., Calo, L., Molinaro, G., Battaglia, G., Maggi, L., Nicoletti, F., Melchiorri, D., Eusebi, F., Massey, P. V. and Bashir, Z. I., 2010. Interaction between ephrins and mGlu5 metabotropic glutamate receptors in the induction of long-term synaptic depression in the hippocampus. Journal of Neuroscience, 30 (8), pp. 2835-2844.

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http://dx.doi.org/10.1523/​JNEUROSCI.4834-09.2010

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 microM) 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 microM DHPG. 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.

Details

Item Type Articles
CreatorsPiccinin, S., Cinque, C., Calo, L., Molinaro, G., Battaglia, G., Maggi, L., Nicoletti, F., Melchiorri, D., Eusebi, F., Massey, P. V. and Bashir, Z. I.
DOI10.1523/​JNEUROSCI.4834-09.2010
DepartmentsFaculty of Science > Pharmacy & Pharmacology
Research CentresCentre for Science Studies (SSC)
RefereedYes
StatusPublished
ID Code23428

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