Activation of group I mGluRs increases spontaneous IPSC frequency in rat frontal cortex.
The effect of metabotropic glutamate receptor (mGluR) activation on inhibitory synaptic transmission was examined by using whole cell patch-clamp recordings. Spontaneous (s) and miniature (m) inhibitory postsynaptic currents (IPSCs) were recorded from visually identified layer II/III pyramidal neurons in rat neocortex in vitro. Excitatory postsynaptic currents (EPSCs) were blocked by using bath application of 20 microM D(-)2-amino-5-phosphonovaleric acid and 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione. In the presence of 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (30-100 microM), Lp4-quisqualate (5 microM), and the group I selective mGluR agonist (S)-3,5-dihydroxyphenylglycine (100 microM), the frequency of sIPSCs was increased. Decay kinetics of sIPSCs were unaffected. No enhancement of mIPSCs was observed. Bath application of group II (2S,3S,4S-alpha-carboxycyclopropyl-glycine; 5 microM) and group III selective mGluR agonists (L-2-amino-4-phosphonobutyric acid; 100 microM) had no detectable effects on the frequency or amplitude of sIPSCs. These findings indicate that activation of group I mGluRs (mGluR1 and/or mGluR5) enhances gamma-aminobutyric acid-mediated synaptic inhibition in layer II/III pyramidal neurons in neocortex. The lack of effect on mIPSCs suggests a presynaptic action via excitation of inhibitory interneurons.
Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0021, USA.
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D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005625:Frontal Lobe / Q000737:chemistry* / Q000502:physiology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D009433:Neural Inhibition / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012118:Resorcinols / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
C089836:2-amino-2-methyl-4-phosphonobutyrate; D000600:Amino Acids, Dicarboxylic; D000613:Aminobutyrates; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C035261:(alpha-carboxycyclopropyl)glycine; D013779:Tetrodotoxin; C079215:3,5-dihydroxyphenylglycine; D016318:Quisqualic Acid; D005998:Glycine