title: Activation of presynaptic group III metabotropic receptors enhances glutamate release in rat entorhinal cortex.
abstract: The role of group III metabotropic glutamate receptors (mGluRs) in modulating excitatory synaptic transmission was investigated in the rat entorhinal cortex (EC) in vitro. AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) were recorded in the whole cell configuration of the patch-clamp technique from visually identified neurons in layers V and II. In layer V, bath application of the specific group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 500 microM) resulted in a marked facilitation of both spontaneous and activity-independent "miniature" (s/mEPSC) event frequency. The facilitatory effect of L-AP4 (100 microM) on sEPSC frequency prevailed in the presence of DL-2-amino-5-phosphonopentanoic acid (100 microM) but was abolished by the group III antagonist (RS)-cyclopropyl-4-phosphonophenylglycine (20 microM). These data confirmed that group III mGluRs, and not N-methyl-D-aspartate (NMDA) receptors were involved in the response to L-AP4. Bath application of the specific mGluR4a agonist (1S,3R,4S)-1-aminocyclopentane-1,2, 4-tricarboxylic acid (20 microM) also had a facilitatory effect on sEPSC frequency, suggesting involvement of mGluR4a. In layer II neurons, L-AP4 caused a reduction in sEPSC frequency but did not affect mEPSCs recorded in the presence of tetrodotoxin. These findings suggest that a group III mGluR with mGluR4a-like pharmacology is involved in modulating synaptic transmission in layer V cells of the EC. The effect on mEPSCs suggests that this receptor is located presynaptically and that its activation results in a direct facilitation of glutamate release. This novel facilitatory effect is specific to layer V and, to our knowledge, is the first report of a direct facilitatory action of group III mGluRs on synaptic transmission. In layer II, L-AP4 had an inhibitory effect on glutamate release similar to that reported in other brain regions.
authors.affiliation: Department of Physiology, School of Medical Sciences, University of Bristol, United Kingdom.
authors.forename: D I
authors.initials: DI
authors.lastname: Evans
authors.forename: R S
authors.initials: RS
authors.lastname: Jones
authors.forename: G
authors.initials: G
authors.lastname: Woodhall
mesh_terms: D000613:Aminobutyrates / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D003517:Cyclopentanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018728:Entorhinal Cortex / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000502:physiology; D014233:Tricarboxylic Acids / Q000494:pharmacology
chemical_list: C409063:1-aminocyclopentane-1,2,4-tricarboxylic acid; C088229:2-amino-4-phosphonobutyrate receptor; D000613:Aminobutyrates; D003517:Cyclopentanes; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D014233:Tricarboxylic Acids; C104331:cyclopropyl-4-phosphonophenylglycine; C102718:metabotropic glutamate receptor 3; D018698:Glutamic Acid; C012729:2-amino-4-phosphonobutyric acid; D005998:Glycine