title: Activity-dependent presynaptic autoinhibition by group II metabotropic glutamate receptors at the perforant path inputs to the dentate gyrus and CA1.
abstract: Pharmacological activation of metabotropic glutamate receptors (mGluRs) can inhibit synaptic transmission; however, relatively little evidence exists regarding the physiological conditions under which such autoreceptors are activated by synaptically released glutamate. Bath application of selective group II mGluR agonists profoundly inhibited field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of the perforant path inputs to both the mid-molecular layer of the dentate gyrus and the stratum lacunosum moleculare of the CA1. Application of the group II selective mGluR antagonist LY341495 resulted in an increase in the relative amplitude of a test fEPSP evoked 200 ms after a conditioning burst, but not after a single conditioning stimulus, in both pathways. Antagonist application also resulted in a marked increase in the relative amplitude of test population spikes evoked in the dentate gyrus following a conditioning burst. These observations are consistent with a presynaptic autoinhibitory action of group II metabotropic receptors that is revealed following burst stimulation of the pathway, consistent with their localisation in the preterminal zone. Activation of group II mGluRs during theta-gamma pattern discharge of projection neurones in the entorhinal cortex is likely to play an important role in the regulation of synaptic transmission and plasticity in the perforant pathway.
authors.affiliation: F. Hoffmann-La Roche Ltd, Pharma Division, Preclinical CNS Research, Building 70/343, CH-4070, Basel, Switzerland. james_n.kew@roche.com
authors.forename: J N
authors.initials: JN
authors.lastname: Kew
authors.forename: J M
authors.initials: JM
authors.lastname: Ducarre
authors.forename: M C
authors.initials: MC
authors.lastname: Pflimlin
authors.forename: V
authors.initials: V
authors.lastname: Mutel
authors.forename: J A
authors.initials: JA
authors.lastname: Kemp
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D009434:Neural Pathways / Q000187:drug effects*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2