Roles for nitric oxide and arachidonic acid in the induction of heterosynaptic cerebellar LTD

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 th e same cell. Inhibitors of NO synthase (7-nitro-indazole), soluble guanylat e cyclase (ODQ) and PKG (KT5823) all prevented depression at each of two in dependent PF pathways to a single PC. Inhibition of NOS also unmasked a pla telet activating factor (PAF)-mediated synaptic potentiation of possible pr esynaptic origin. LTD was also prevented by the phospholipase A(2) inhibito r OBAA but was rescued by co-perfusion with arachidonic acid. We conclude t hat NO and diffusible products of phospholipase A(2) metabolism are potenti al mediators of the spread of cerebellar plasticity at the single cell leve l. NeuroReport 12:133-136 (C) 2001 Lippincott Williams & Wilkins.