Different metabotropic glutamate receptors play opposite roles in synaptic plasticity of the rat medial vestibular nuclei.
In the medial vestibular nuclei (MVN) of rat brainstem slices, the role of group II and III metabotropic glutamate receptors (mGluRs) and of the subtypes of group I mGluRs: mGluR1, mGluR5, was investigated in basal synaptic transmission and in the induction and maintenance of long-term potentiation (LTP). We used selective antagonists and agonists for mGluRs and we analysed the field potentials evoked by vestibular afferent stimulation before and after high-frequency stimulation (HFS) to induce LTP. The group II and III mGluR antagonist, (R,S)-alpha-2-methyl-4sulphonophenylglycine (MSPG), induced LTP per se and caused a reduction of the paired-pulse facilitation (PPF) ratio indicating an enhancement of glutamate release. This suggests that group II and III mGluRs are activated under basal conditions to limit glutamate release. Both the group II and III mGluR selective antagonists, 2S-2-amino-2-(1S,2S-2-carboxycycloprop-1-yl)-3-(xanth-9-yl)propanoate (LY341495) and (R,S)-alpha-methylserine-O-phosphate (MSOP), induced LTP, and the selective agonists, (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) depressed the field potentials and prevented HFS-LTP, with a prevailing contribution of group II mGluRs over that of group III mGluRs. The mGluR1 antagonist, 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt) prevented the full development and maintenance of HFS-LTP. By contrast, the mGluR5 antagonist, 2-methyl-6-phenylethynylpyridine (MPEP) induced LTP per se, which was impeded by CPCCOEt, and it had no effect on LTP once induced by HFS. The PPF analysis showed an enhancement of glutamate release during MPEP potentiation. The group I mGluR agonist, (R,S)-3,5-dihydroxyphenylglycine (DHPG) induced LTP per se, which was blocked by CPCCOEt. By contrast the mGluR5 agonist, (R,S)-2-chloro-5-hydroxypheylglycine (CHPG) prevented LTP elicited by HFS and DHPG as well. In conclusion vestibular LTP is inhibited by group II and III mGluRs during the early induction phase while it is facilitated by mGluR1 for achieving its full expression and consolidation. An additional inhibitory control is exerted by mGluR5 at the level of this facilitatory phase.
Grassi
Silvarosa
S
Department of Internal Medicine, Section of Human Physiology, University of Perugia, Perugia I-06100, Italy. isfisuma@unipg.it
Frondaroli
Adele
A
Pettorossi
Vito Enrico
VE
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002867:Chromones / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D010648:Phenylacetates / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012118:Resorcinols / Q000494:pharmacology; D014726:Vestibular Nuclei / Q000502:physiology*; D014966:Xanthenes / Q000494:pharmacology
C107349:2-chloro-5-hydroxyphenylglycine; C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; D000596:Amino Acids; D002867:Chromones; D018691:Excitatory Amino Acid Antagonists; C578935:GRM5 protein, human; C578937:Grm5 protein, rat; C114624:LY 341495; D010648:Phenylacetates; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C104077:metabotropic glutamate receptor type 1; C079215:3,5-dihydroxyphenylglycine; C121465:6-methyl-2-(phenylethynyl)pyridine; D005998:Glycine