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J Neurophysiol 86: 2405-2412, 2001;
0022-3077/01 $5.00
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The Journal of Neurophysiology Vol. 86 No. 5 November 2001, pp. 2405-2412
Copyright ©2001 by the American Physiological Society

Activation of Group I mGluRs Is Necessary for Induction of Long-Term Depression at Striatal Synapses

Ki-Wug Sung,1 Sukwoo Choi,2 and David M. Lovinger3

 1Department of Pharmacology, College of Medicine, Catholic University, Seoul 137-701;  2Department of Neuroscience, School of Medicine, Ewha Institute for Neuroscience, Ewha Women's University, Seoul 110-783, Korea; and  3Department of Molecular Physiology and Biophysics, Vanderbilt University Medical School, Nashville, Tennessee 37232

Sung, Ki-Wug, Sukwoo Choi, and David M. Lovinger. Activation of Group I mGluRs Is Necessary for Induction of Long-Term Depression at Striatal Synapses. J. Neurophysiol. 86: 2405-2412, 2001. Activation of metabotropic glutamate receptors (mGluRs), which are coupled to G proteins, has important roles in certain forms of synaptic plasticity including corticostriatal long-term depression (LTD). In the present study, extracellular field potential and whole cell voltage-clamp recording techniques were used to investigate the effect of mGluR antagonists with different subtype specificity on high-frequency stimulation (HFS)-induced LTD of synaptic transmission in the striatum of brain slices obtained from 15-to 25-day-old rats. Induction of LTD was prevented during exposure to the nonselective mGluR antagonist (RS)-alpha -methyl-4-carboxyphenylglycine (500 µM). The group I mGluR-selective antagonists (S)-4-carboxy-phenylglycine (50 µM) and (RS)-1-aminoindan-1,5-dicarboxylic acid (100 µM) prevented induction of LTD when applied before and during HFS. The mGluR1-selective antagonist 7-(Hydroxyimino) cyclopropa[b]chromen-1a-carboxylate ethyl ester (80 µM) also blocked LTD induction. Unexpectedly, the mGluR5-selective antagonist 2-methyl-6-(phenylethyl)-pyridine (10 µM) also prevented LTD induction. The group II mGluR antagonist LY307452 (10 µM) did not block LTD induction at corticostriatal synapses, but LY307452 was able to block transient synaptic depression induced by the group II agonist LY314593. None of the antagonists had any effect on basal synaptic transmission at the concentrations used, and mGluR antagonists did not reverse LTD when applied beginning 20 min after HFS. These results suggest that both group I mGluR subtypes contribute to the induction of LTD at corticostriatal synapses.




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