title: Reduction of excitatory postsynaptic responses by persistently active metabotropic glutamate receptors in the hippocampus.
abstract: The release of glutamate from axon terminals is under the control of a variety of presynaptic receptors, including several metabotropic glutamate receptors (mGluRs). Synaptically released glutamate can activate mGluRs within the same synapse where it was released and also at a distance following its diffusion from the synaptic cleft. It is unknown, however, whether the release of glutamate is under the control of persistently active mGluRs. We tested the contribution of mGluR activation to the excitatory postsynaptic responses recorded from several types of GABAergic interneuron in strata oriens/alveus of the mouse hippocampus. The application of 1 microM (alphaS)-alpha-amino-alpha-[(1S,2S)-2-carboxycyclopropyl]xanthine-9-propanoic acid (LY341495), a broad-spectrum mGluR (subtypes 2/3/7/8) antagonist at this concentration, increased evoked-excitatory postsynaptic current (eEPSC) amplitudes by 60% (n = 33). On identified cell types, LY341495 had either no effect (7 of 14 basket and 7 of 13 oriens-lacunosum moleculare, O-LM cells) or resulted in a 32 +/- 30% (mean +/- SD) increase in EPSC amplitudes recorded from basket cells and a seven-times greater (216 +/- 102%) enhancement of EPSCs in O-LM cells. The enhancement of the first EPSC of a high-frequency train indicates persistent mGluR activation. During antagonist application, the relative increase in EPSC amplitude evoked by the second and subsequent pulses in the train was not larger than that of the first EPSC, showing no further receptor activation by the released transmitter. The effect of mGluR subtype selective agonists [3 microM L(+)-2-amino-4-phosphonobutyric acid (L-AP4): mGluR4/8; 600 microM L-AP4: mGluR4/7/8; 1 microM (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IU): mGluR2/3] and an antagonist (0.2 microM LY341495: mGluR2/3/8) suggests that persistently active mGluR2/3/8 control the excitability of hippocampal network.
authors.affiliation: Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, 1083 Budapest, Hungary; and Medical Research Council, Anatomical Neuropharmacology Unit, University Department of Pharmacology, Oxford OX1 3TH, United Kingdom.
authors.forename: Attila
authors.initials: A
authors.lastname: Losonczy
authors.forename: Peter
authors.initials: P
authors.lastname: Somogyi
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Nusser
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007395:Interneurons / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology; D011422:Propionates / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D014966:Xanthenes / Q000494:pharmacology
chemical_list: C114785:2-amino-4-phosphono-propinate; D000596:Amino Acids; D000927:Anticonvulsants; D003521:Cyclopropanes; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D011422:Propionates; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D005998:Glycine