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

Brain Res. 2004 Oct 1;1022(1-2):12-8. doi: 10.1016/j.brainres.2004.06.060.

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 microM, 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 (p70(S6K)) at Thr3889, a major regulator of translation required for the induction of protein synthesis-dependent forms of LTP.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Benzoates / pharmacology
  • Dendrites / drug effects
  • Dendrites / metabolism
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Excitatory Postsynaptic Potentials / radiation effects
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Immunohistochemistry / methods
  • In Vitro Techniques
  • Long-Term Potentiation / physiology*
  • Long-Term Potentiation / radiation effects
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / radiation effects
  • Phosphorylation / drug effects
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / physiology*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Threonine / metabolism
  • Time Factors

Substances

  • Benzoates
  • Excitatory Amino Acid Antagonists
  • Grm5 protein, mouse
  • Grm5 protein, rat
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • alpha-methyl-4-carboxyphenylglycine
  • Threonine
  • 6-methyl-2-(phenylethynyl)pyridine
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Glycine