title: Evidence that glutamate acting on presynaptic type-II metabotropic glutamate receptors alone does not fully account for the phenomenon of depolarisation-induced suppression of inhibition in cerebellar Purkinje cells.
abstract: Depolarisation-induced suppression of inhibition (DSI) is a form of short-term synaptic plasticity at gamma-aminobutyric-acid-(GABA)ergic synapses between principal neurons and interneurons in both the cerebellum and the hippocampus. The induction of DSI involves an intracellular calcium-dependent release of a retrograde messenger from the postsynaptic principal neuron (Purkinje cell/pyramidal cell in cerebellum/hippocampus) onto presynaptic interneurons, where it is thought to bind to guanine nucleotide-binding protein (G protein)-coupled receptors and subsequently reducing GABA release from these interneurons onto the postsynaptic principal neuron. Pharmacological studies have indicated that glutamate might be a retrograde messenger in both cerebellum and hippocampus, where, in the former at least, it seems to activate type-II metabotropic glutamate receptors (mGluRs). Using LY-341495, a recently described, highly specific and potent antagonist of type-II mGluRs, to block these receptors reduced DSI slightly, but significantly, in spite of the fact that this antagonist completely suppressed the effects of stimulating type-II mGluRs with a specific agonist. Activation of type II mGluRs alone thus cannot account fully for DSI in cerebellum and hence other mechanisms are involved in its induction. Such mechanisms probably involve an additional retrograde signal.
authors.affiliation: University Laboratory of Physiology, Oxford University, UK. maike.glitsch@physiol.ox.ac.uk
authors.forename: M D
authors.initials: MD
authors.lastname: Glitsch
authors.forename: J J
authors.initials: JJ
authors.lastname: Jack
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D009433:Neural Inhibition / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D018094:Receptors, Metabotropic Glutamate; D017661:Receptors, Presynaptic; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; D018698:Glutamic Acid