Presynaptic and postsynaptic effects of nitric oxide donors at synapses between parallel fibres and Purkinje cells: involvement in cerebellar long-term depression.

The involvement of nitric oxide in cerebellar long-term depression is widely accepted. Nevertheless, its site of action has remained unclear. Using the coefficient of variation method applied to the parallel fibre-mediated excitatory postsynaptic currents recorded in voltage-clamped Purkinje cells. this study shows that nitric oxide donors exert their effects at both presynaptic and postsynaptic sites. The presynaptic depression fades away with washout of nitric oxide donors and is mediated through the potentiation of A1 adenosine receptors. Part of this effect may be due to non-nitric oxide products. In contrast, long-term depression induced by nitric oxide donors is expressed at a postsynaptic site, and is independent of the ADP ribosylation. Long-term depression induced by pairing is also expressed mainly at a postsynaptic level. These results establish that long-term depression at the parallel fibre Purkinje cell synapse induced by pairing of nitric oxide donors is mostly expressed at a postsynaptic site.