The metabotropic glutamate receptor 5 is necessary for late-phase long-term potentiation in the hippocampal CA1 region.
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.
Francesconi
Walter
W
Department of Neuropharmacology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA, USA. WFRANC@SCRIPPS.EDU
Cammalleri
Maurizio
M
Sanna
Pietro Paolo
PP
D000818:Animals; D000831:Animals, Newborn; D001565:Benzoates / Q000494:pharmacology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D013912:Threonine / Q000378:metabolism; D013997:Time Factors
D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; C578936:Grm5 protein, mouse; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C079694:alpha-methyl-4-carboxyphenylglycine; D013912:Threonine; C121465:6-methyl-2-(phenylethynyl)pyridine; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D005998:Glycine