Long-term depression requires nitric oxide and guanosine 3':5' cyclic monophosphate production in rat cerebellar Purkinje cells.

In patch-clamped Purkinje cells, bath application of the nitric oxide synthase inhibitor NG-methyl-L-arginine consistently prevents the induction of long-term depression (LTD) of parallel fibre-mediated excitatory postsynaptic potentials (EPSPs) induced by their pairing with calcium spikes. On the other hand, bath application of nitric oxide donors and of 8-bromoguanosine 3':5' cyclic monophosphate is able to reproduce an LTD-like phenomenon. LTD of parallel fibre-mediated EPSPs also occurs when nitric oxide donors or guanosine 3':5' cyclic monophosphate are directly dialysed into Purkinje cells, and this effect partially occludes LTD induced by pairing protocols. These results show that nitric oxide does play a role in LTD induction, and demonstrate for the first time that its site of action is probably the soluble guanylate cyclase of Purkinje cells.