title: Antagonists reversibly reverse chemical LTD induced by group I, group II and group III metabotropic glutamate receptors.
abstract: Metabotropic glutamate (mGlu) receptors are implicated in many neurological and psychiatric diseases and are the targets of therapeutic agents currently in clinical development. Their activation has diverse effects in the central nervous system (CNS) that includes an involvement in synaptic plasticity. We previously reported that the brief exposure of hippocampal slices to dihydroxyphenylglycine (DHPG) can result in a long-term depression (LTD) of excitatory synaptic transmission. Surprisingly, this LTD could be fully reversed by mGlu receptor antagonists in a manner that was itself fully reversible upon washout of the antagonist. Here, 15 years after the discovery of DHPG-LTD and its reversible reversibility, we summarise these initial findings. We then present new data on DHPG-LTD, which demonstrates that evoked epileptiform activity triggered by activation of group I mGlu receptors can also be reversibly reversed by mGlu receptor antagonists. Furthermore, we show that the phenomenon of reversible reversibility is not specific to group I mGlu receptors. We report that activation of group II mGlu receptors in the temporo-ammonic pathway (TAP) and mossy fibre pathway within the hippocampus and in the cortical input to neurons of the lateral amygdala induces an LTD that is reversed by LY341495, a group II mGlu receptor antagonist. We also show that activation of group III mGlu8 receptors induces an LTD at lateral perforant path inputs to the dentate gyrus and that this LTD is reversed by MDCPG, an mGlu8 receptor antagonist. In conclusion, we have shown that activation of representative members of each of the three groups of mGlu receptors can induce forms of LTD than can be reversed by antagonists, and that in each case washout of the antagonist is associated with the re-establishment of the LTD. This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'.
authors.affiliation: Centre for Synaptic Plasticity, School of Physiology and Pharmacology, Dorothy Hodgkin Building, University of Bristol, Bristol BS1 3NY, UK. David.Lodge@Bristol.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Lodge
authors.forename: Patrick
authors.initials: P
authors.lastname: Tidball
authors.forename: Marion S
authors.initials: MS
authors.lastname: Mercier
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Lucas
authors.forename: Lydia
authors.initials: L
authors.lastname: Hanna
authors.forename: Laura
authors.initials: L
authors.lastname: Ceolin
authors.forename: Minos
authors.initials: M
authors.lastname: Kritikos
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Fitzjohn
authors.forename: John L
authors.initials: JL
authors.lastname: Sherwood
authors.forename: Neil
authors.initials: N
authors.lastname: Bannister
authors.forename: Arturas
authors.initials: A
authors.lastname: Volianskis
authors.forename: David E
authors.initials: DE
authors.lastname: Jane
authors.forename: Zuner A
authors.initials: ZA
authors.lastname: Bortolotto
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
mesh_terms: D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D014966:Xanthenes / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D018691:Excitatory Amino Acid Antagonists; C114624:LY 341495; D018094:Receptors, Metabotropic Glutamate; D014966:Xanthenes; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; C104077:metabotropic glutamate receptor type 1; D005998:Glycine
keywords: DCG-IV; DHPG; Long-term depression; Metabotropic glutamate receptors; mGlu1; mGlu2; mGlu5; mGlu8