title: Roles for nitric oxide and arachidonic acid in the induction of heterosynaptic cerebellar LTD.
abstract: In cerebellar slices conjunctive pairing of parallel fibre (PF) stimulation with depolarization of Purkinje cells (PCs) induces a long-term depression (LTD) of PF synaptic transmission that spreads to unpaired PF inputs to the same cell. Inhibitors of NO synthase (7-nitro-indazole), soluble guanylate cyclase (ODQ) and PKG (KT5823) all prevented depression at each of two independent PF pathways to a single PC. Inhibition of NOS also unmasked a platelet activating factor (PAF)-mediated synaptic potentiation of possible presynaptic origin. LTD was also prevented by the phospholipase A2 inhibitor OBAA but was rescued by co-perfusion with arachidonic acid. We conclude that NO and diffusible products of phospholipase A2 metabolism are potential mediators of the spread of cerebellar plasticity at the single cell level.
authors.affiliation: The Pharmaceutical Science Research Institute, Division of Life and Health Sciences, Aston University, Birmingham, UK.
authors.forename: T
authors.initials: T
authors.lastname: Reynolds
authors.forename: N A
authors.initials: NA
authors.lastname: Hartell
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000502:physiology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D010069:Oxadiazoles / Q000494:pharmacology; D010741:Phospholipases A / Q000187:drug effects / Q000378:metabolism*; D054467:Phospholipases A2; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D007191:Indazoles; D010069:Oxadiazoles; D011810:Quinoxalines; D016718:Arachidonic Acid; D009569:Nitric Oxide; D010741:Phospholipases A; D054467:Phospholipases A2; C080122:7-nitroindazole