CLIMBING FIBERS AS A SOURCE OF NITRIC-OXIDE IN THE CEREBELLUM

Exposure of adult rat cerebellar slices to a moderately raised K+ concentration (15 mM) caused a large (30-fold) rise in the levels of cyclic GMP. Excitatory amino acid antagonists failed to inhibit this response, nor could it be mimicked by agonists active at a number of other transmitter receptors. It was, however, inhibited by the nitric oxide (NO) synthase antagonist, L-methylarginine (IC50 = 10-mu-M), and also by tetrodotoxin (1-mu-M) implying that underlying the cyclic GMP response was an action potential-dependent formation of NO. Prelesioning of climbing fibres resulted in a loss of approximately 50% of the response to K+ but failed to influence the effects of glutamate receptor agonists or the NO-donor, nitroprusside. These findings point to a new mechanism for the formation of NO in the central nervous system and suggest that, in the cerebellum, climbing fibres are a source of NO.