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

S Piccinin, C Cinque, L Calo, G Molinaro, G Battaglia, L Maggi, F Nicoletti, D Melchiorri, F Eusebi, Peter V Massey, Z I Bashir

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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.
Original languageEnglish
Pages (from-to)2835-2844
Number of pages10
JournalJournal of Neuroscience
Volume30
Issue number8
DOIs
Publication statusPublished - 2010

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Long-Term Synaptic Depression
Ephrins
Metabotropic Glutamate Receptors
Hippocampus
EphB1 Receptor
Synaptic Transmission
EphA1 Receptor
Excitatory Amino Acid Agonists
Synapses
Esters
dihydroxyphenylethylene glycol
Pharmacology
Pharmaceutical Preparations

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Interaction between ephrins and mGlu5 metabotropic glutamate receptors in the induction of long-term synaptic depression in the hippocampus. / Piccinin, S; Cinque, C; Calo, L; Molinaro, G; Battaglia, G; Maggi, L; Nicoletti, F; Melchiorri, D; Eusebi, F; Massey, Peter V; Bashir, Z I.

In: Journal of Neuroscience, Vol. 30, No. 8, 2010, p. 2835-2844.

Research output: Contribution to journalArticle

Piccinin, S, Cinque, C, Calo, L, Molinaro, G, Battaglia, G, Maggi, L, Nicoletti, F, Melchiorri, D, Eusebi, F, Massey, PV & Bashir, ZI 2010, 'Interaction between ephrins and mGlu5 metabotropic glutamate receptors in the induction of long-term synaptic depression in the hippocampus', Journal of Neuroscience, vol. 30, no. 8, pp. 2835-2844. https://doi.org/10.1523/​JNEUROSCI.4834-09.2010
Piccinin, S ; Cinque, C ; Calo, L ; Molinaro, G ; Battaglia, G ; Maggi, L ; Nicoletti, F ; Melchiorri, D ; Eusebi, F ; Massey, Peter V ; Bashir, Z I. / Interaction between ephrins and mGlu5 metabotropic glutamate receptors in the induction of long-term synaptic depression in the hippocampus. In: Journal of Neuroscience. 2010 ; Vol. 30, No. 8. pp. 2835-2844.
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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 (Cal{\`o} 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.",
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AU - Piccinin, S

AU - Cinque, C

AU - Calo, L

AU - Molinaro, G

AU - Battaglia, G

AU - Maggi, L

AU - Nicoletti, F

AU - Melchiorri, D

AU - Eusebi, F

AU - Massey, Peter V

AU - Bashir, Z I

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