THE NITRIC-OXIDE CYCLIC-GMP PATHWAY AND SYNAPTIC DEPRESSION IN RAT HIPPOCAMPAL SLICES

The ability of exogenous nitric oxide (NO) to modify synaptic transmis sion was investigated in area CA1 of the rat hippocampal slice. The NO donors S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathion e (SNOG) depressed field excitatory postsynaptic potentials evoked by low frequency stimulation of the Schaffer collateral - commissural pat hway. Upon washout of the NO donors, synaptic transmission rapidly ret urned to control levels. A similar reversible synaptic depression was produced by SNAP when tetanic stimulation (100 Hz; 1 s) was delivered in its presence. The effect of SNAP was not mimicked by its precursor or breakdown product and was blocked by haemoglobin, indicating that t he effect involved NO, Roussin's black salt, a photolabile NO donor, a lso depressed transiently field excitatory postsynaptic potentials fol lowing photolysis. The depression was induced rapidly following a flas h of UV light (20 s duration) focused onto the slice using a confocal microscope. The depressant effect of the NO donors on synaptic transmi ssion was mimicked by zaprinast, a specific cGMP - phosphodiesterase i nhibiter. Zaprinast depressed to a similar extent both the alpha-amino -3-hydroxy-5-methyl-4-isoxazole propionate and N-methyl-D-aspartate re ceptor-mediated components of excitatory postsynaptic currents without affecting passive membrane properties, indicating a presynaptic locus of action. SNAP, SNOG and zaprinast all elevated cGMP levels in rat h ippocampal slices. Immunocytochemical staining revealed that the cGMP accumulation was mainly in a network of varicose fibres running throug hout the CA1 region, consistent with a presynaptic site of action of N O. We conclude that NO, possibly through activation of guanylate cycla se, may be involved in transient presynaptic depression in the CA1 reg ion of the hippocampus.