Dual modulation of synaptic inhibition by distinct metabotropic glutamate receptors in the rat hippocampus.
1. The effects of metabotropic glutamate receptor (mGluR) activation on synaptic inhibition were examined using whole-cell recordings of spontaneous and miniature inhibitory synaptic currents from CA3 pyramidal cells in rat hippocampal slices. 2. The mGluR agonist (1S,3R)trans-1-aminocyclopentane-1,3-dicarboxylic acid (tACPD) increased spontaneous IPSC (spIPSC) frequency by up to 5-fold. At doses above 5 microM the increase was transient (15-45 s) and was followed by a decline to control frequency. In these conditions, elevating external K+ from 2 to 8 mM could still increase spIPSC frequency. 3. Miniature IPSCs (mIPSCs) were recorded in the presence of 1 microM TTX, 5 mM Mg2+ and nominally zero Ca2+. At concentrations above 50 microM, tACPD induced a sustained, reversible reduction in mIPSC frequency by up to 43%. 4. Quisqualate, at doses as low as 50 nM, increased spIPSC frequency, but did not affect mIPSC frequency at concentrations up to 10 microM. 5. The specific mGluR2 and 3 agonist (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV, 3 microM) reduced mIPSC frequency by 40 +/- 4% but did not increase spIPSC frequency. 6. The putative mGluR antagonist L-2-amino-3-phosphonopropionate (L-AP3, 1 mM) blocked the effect of tACPD on mIPSC but not spIPSC frequency. The broad-spectrum antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM) blocked both responses. 7. mGluR activation also had dual effects on IPSCs evoked by focal extracellular stimulation. Application of 5 microM tACPD increased the mean amplitude of evoked IPSCs by 112 +/- 9%, largely by reducing the proportion of response failures. In contrast, IPSC amplitude was reduced to 44 +/- 1% of control values by 3 microM DCG-IV. 8. These results suggest hippocampal inhibitory cells express two distinct mGluR subtypes. One receptor (possibly mGluR1 or 5) is located on somato-dendritic membrane and enhances cell excitability. Another (mGluR2 or 3) is present at inhibitory terminals and reduces the probability of GABA release.
Poncer
J C
JC
Laboratoire de Neurobiologie Cellulaire, Institut Pasteur, Paris, France.
Shinozaki
H
H
Miles
R
R
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D007700:Kinetics; D009498:Neurotoxins / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D009498:Neurotoxins; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid