title: Functional and ultrastructural analysis of group I mGluR in striatal fast-spiking interneurons.
abstract: Striatal parvalbumin-containing fast-spiking (FS) interneurons provide a powerful feedforward GABAergic inhibition on spiny projection neurons, through a widespread arborization and electrical coupling. Modulation of FS interneuron activity might therefore strongly affect striatal output. Metabotropic glutamate receptors (mGluRs) exert a modulatory action at various levels in the striatum. We performed electrophysiological recordings from a rat striatal slice preparation to investigate the effects of group I mGluR activation on both the intrinsic and synaptic properties of FS interneurons. Bath-application of the group I mGluR agonist, (S)-3,5-dihydroxyphenylglycine (3,5-DHPG), caused a dose-dependent depolarizing response. Both (S)-(+)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385) and 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester (CPCCOEt), selective mGluR1 antagonists, significantly reduced the amplitude of the membrane depolarization caused by 3,5-DHPG application. Conversely, mGluR5 antagonists, 2-methyl-6-(phenylethylnyl)pyridine hydrochloride (MPEP) and 6-methyl-2-(phenylazo)-3-pyridinol (SIB1757), were unable to affect the response to 3,5-DHPG, suggesting that only mGluR1 contributes to the 3,5-DHPG-mediated excitatory action on FS interneurons. Furthermore, mGluR1 blockade significantly decreased the amplitude of the glutamatergic postsynaptic potentials, whereas the mGluR5 antagonist application produced a small nonsignificant inhibitory effect. Surprisingly, our electron microscopic data demonstrate that the immunoreactivity for both mGluR1a and mGluR5 is expressed extrasynaptically on the plasma membrane of parvalbumin-immunoreactive dendrites of FS interneurons. Together, these results suggest that despite a common pattern of distribution, mGluR1 and mGluR5 exert distinct functions in the modulation of FS interneuron activity.
authors.affiliation: Fondazione Santa Lucia I.R.C.C.S., Department of Neuroscience, Clinica Neurologica, University Tor Vergata, Via Montpellier, 00133 Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bonsi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sciamanna
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Mitrano
authors.forename: Dario
authors.initials: D
authors.lastname: Cuomo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Paola
authors.initials: P
authors.lastname: Platania
authors.forename: Yoland
authors.initials: Y
authors.lastname: Smith
authors.forename: Antonio
authors.initials: A
authors.lastname: Pisani
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D010320:Parvalbumins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010320:Parvalbumins; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D001640:Bicuculline