Presynaptic N-methyl-d-aspartate receptors at the parallel fiber–Purkinje cell synapse

At the cerebellar synapse between the parallel fibers (PFs) and the Purkinje cells in the cerebellum, we have found that application of N-methyl-d-aspartate (NMDA) reversibly depresses the postsynaptic current. We present evidence that this depression involves NMDA receptors located on the presynaptic axons and requires that the NMDA application be combined with action potentials in the PFs. Unexpectedly, unlike other modulations mediated by presynaptic receptors, the NMDA-induced inhibition does not involve a depression of transmitter release. Because it is blocked by both nitric oxide synthase and soluble guanylate cyclase inhibitors, we propose that it involves a trans-synaptic mechanism in which NO released by the PFs decreases the glutamate sensitivity of the Purkinje cell.