Selective antagonists of the metabotropic receptors 1 (mGluR1), F2-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 mM, 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 synthesisdependent forms of LTP.
The metabotropic glutamate receptor 5 is necessary for late-phase long-term potentiation in the hippocampal CA1 region
CAMMALLERI, MAURIZIOSecondo
;
2004-01-01
Abstract
Selective antagonists of the metabotropic receptors 1 (mGluR1), F2-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 mM, 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 synthesisdependent forms of LTP.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
