Depression of GABAergic input to identified hippocampal neurons by group III metabotropic glutamate receptors in the rat.
The release of GABA in synapses is modulated by presynaptic metabotropic glutamate receptors (mGluRs). We tested whether GABA release to identified hippocampal neurons is influenced by group III mGluR activation using the agonist L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) on inhibitory postsynaptic currents (IPSCs) evoked in CA1 interneurons and pyramidal cells. In interneurons, characterized with biocytin and immunolabelling for somatostatin, evoked IPSCs were depressed by 50 micro m L-AP4 (activating mGluR4 and 8) to 68 +/- 6% of control, but they were rarely depressed in pyramidal cells (96 +/- 4% of control). At 300-500 micro m concentration (activating mGluR4, 7 and 8), L-AP4 depressed IPSCs in both interneurons (to 70 +/- 6%) and pyramidal cells (to 67 +/- 4%). The change in trial-to-trial variability and in paired-pulse depression indicated a presynaptic action. In interneurons, the degree of IPSC depression was variable (to 9-87%), and a third of IPSCs were not affected by L-AP4. The L-AP4-evoked IPSC depression was blocked by LY341495. The depression of IPSCs was similar in O-LM cells and other interneurons. The lack of cell-type selectivity and the similar efficacy of different concentrations of L-AP4 suggest that several group III mGluRs are involved in the depression of IPSCs. Electron microscopic immunocytochemistry confirmed that mGluR4, mGluR7a and mGluR8a occur in the presynaptic active zone of GABAergic terminals on interneurons, but not on those innervating pyramidal cells. The high variability of L-AP4-evoked IPSC suppression is in line with the selective expression of presynaptic mGluRs by several distinct types of GABAergic neuron innervating each interneuron type.
Kogo
Naoki
N
Medical Research Council, Anatomical Neuropharmacology Unit, University Department of Pharmacology, Mansfield Road, Oxford, UK.
Dalezios
Yannis
Y
Capogna
Marco
M
Ferraguti
Francesco
F
Shigemoto
Ryuichi
R
Somogyi
Peter
P
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D006735:Horseradish Peroxidase / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007395:Interneurons / Q000145:classification / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D016253:Microscopy, Immunoelectron / Q000379:methods; D009433:Neural Inhibition / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011422:Propionates / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism* / Q000648:ultrastructure; D013004:Somatostatin / Q000378:metabolism; D018709:Statistics, Nonparametric; D013569:Synapses / Q000187:drug effects / Q000648:ultrastructure; D013997:Time Factors; D014966:Xanthenes / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C114785:2-amino-4-phosphono-propinate; D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D011422:Propionates; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C102718:metabotropic glutamate receptor 3; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D015763:2-Amino-5-phosphonovalerate; D006735:Horseradish Peroxidase; C013411:biocytin; D008239:Lysine