Elsevier

Brain Research

Volume 1022, Issues 1–2, 1 October 2004, Pages 12-18
Brain Research

Research report
The metabotropic glutamate receptor 5 is necessary for late-phase long-term potentiation in the hippocampal CA1 region

https://doi.org/10.1016/j.brainres.2004.06.060Get rights and content

Abstract

Selective antagonists of the metabotropic receptors 1 (mGluR1), ±2-methyl-4-carboxyphenylglycine (LY367385), and mGluR5, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), were used to investigate the role of group I metabotropic receptors in late-phase long-term potentiation (L-LTP) at Schaffer collateral/commissural fiber-CA1 synapses in rat hippocampal slices. L-LTP was induced with three trains of tetanization of 1 s duration at 100 Hz separated by 10-min intervals. Neither LY367385 nor MPEP affected basal synaptic responses at the doses used (200 and 10 μM, respectively) and only the mGluR5 inhibitor MPEP blocked L-LTP. However, in agreement with previous mouse mutant studies, we found that both LY367385 and MPEP inhibited the induction of an LTP obtained with a single train of tetanization of 1 s duration at 100 Hz. MPEP's ability to disrupt L-LTP was not due to an effect on NMDA responses since it did not affect pharmacologically isolated N-methyl-d-aspartate (NMDA) excitatory postsynaptic potentials (EPSPs). However, MPEP prevented the increased phosphorylation in dendrites of p70 S6 kinase (p70S6K) at Thr3889, a major regulator of translation required for the induction of protein synthesis-dependent forms of LTP.

Section snippets

Electrophysiological techniques

Hippocampal slices were prepared as previously described [26], [27]. Briefly, Wistar rats (28–35 days of age) were decapitated under halothane anesthesia. Brains were rapidly transferred into ice-cold artificial cerebrospinal fluid (ACSF) (130 mM NaCl; 3.5 mM KCl; 24 mM NaHCO3; 1.25 mM NaH2PO4; 2.2 mM CaCl2; 10 mM glucose; 2 mM MgSO4, oxygenated with a mixture of 95% O2/5% CO2, pH 7.4) and transverse hippocampal slices (400 μm) were obtained with a Leica (Wetzlar, Germany) VT1000E automatic

Results

The role of group I metabotropic glutamate receptors on the induction of L-LTP [11] of fEPSP at Schaffer collateral/commissural fiber-CA1 synapses was investigated in rat hippocampal slices with selective pharmacological inhibitors. A transient application (10 min) of the mGluR5-selective inhibitor MPEP (10 μM) during the L-LTP induction paradigm resulted in a much reduced level of potentiation (Fig. 1A). In fact, the fEPSP slopes following application of MPEP during tetanization were 136.7%

Discussion

We have shown here that mGluR5, but not mGluR1, is required for the induction of L-LTP. We have also observed that both mGluR1 and mGluR5 are required for protein synthesis-independent LTP obtained with a single train of tetanization at 100 Hz. The latter is in good agreement with some previous mouse mutant studies in the literature [1], [15] (but see Ref. [10]). The present findings are also in agreement with the work of Rodriguez et al. [23], who showed that MPEP impairs NMDAR-dependent

Acknowledgments

Supported by NIMH. We are grateful to Dr. Paul Kenny of TSRI for critical review of the manuscript. We are also grateful to Alvin King of TSRI for technical help and to Tom Deerinck and Mark Ellisman of the National Center for Microscopy and Imaging Research at the University of California, San Diego, for their expert assistance with confocal microscopy.

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