Effect of nitric oxide synthase inhibition on long-term potentiation at associational-commissural and mossy fibre synapses on CA3 pyramidal neurones.

1. The sensitivity of long-term potentiation (LTP) to nitric oxide synthase (NOS) inhibition was determined for two synaptic input systems onto CA3 pyramidal neurones the LTP of which display differential sensitivity to N-methyl-D-aspartate (NMDA) receptor antagonists: the fimbrial input which activates the associational-commissural synapses on the distal apical dendrites and the mossy fibre input which synapses on the proximal apical dendrites of CA3 pyramidal neurones. 2. Following high-frequency stimulation (HFS) of the fimbrial input, average e.p.s.p. amplitude increased by 92.4 +/- 22.0% (mean +/- s.e.mean; n = 6 cells) when compared to the pre-HFS average. In the presence of 100 microM N omega-nitro-L-arginine methyl ester (L-NAME), the enhancement was reduced significantly to 32.2 +/- 11.6% (n = 5 cells; P < 0.05). In the presence of 300 microM L-NAME, the inhibition was more complete, with post-HFS e.p.s.p. amplitude increasing an average 6.2 +/- 9.3% (n = 7 cells, P < 0.05). 3. Following high frequency stimulation of the mossy fibre input, average e.p.s.p. amplitude increased by 57.9 +/- 13.0% (n = 6 cells) when compared to the pre-HFS average. The presence of 100 microM L-NAME had no significant effect on the enhancement, averaging 63.6 +/- 5.9% (n = 4 cells; P > 0.05). Similarly, increasing the concentration of L-NAME to 300 microM had no significant effect on the potentiation, with the post-HFS amplitude increasing by an average 55.6 +/- 9.5% (n = 5 cells, P > 0.05). 4. These results suggest that LTP at associational-commissural synapses (fimbrial input) is significantly depressed in the presence of the NOS inhibitor L-NAME, while mossy fibre LTP is unchanged.