Functional and ultrastructural analysis of group I mGluR in striatal fast-spiking interneurons |
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Authors: | Bonsi Paola Sciamanna Giuseppe Mitrano Darlene A Cuomo Dario Bernardi Giorgio Platania Paola Smith Yoland Pisani Antonio |
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Institution: | Fondazione Santa Lucia I.R.C.C.S., Department of Neuroscience, Clinica Neurologica, University Tor Vergata, Via Montpellier, 00133 Rome, Italy. |
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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)cyclopropab]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. |
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Keywords: | GABAergic interneuron mGluR1 mGluR5 rat striatum |
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