The effects of cyanide on neural and synaptic function in hippocampal slices

Transverse slices from guinea pig hippocampi were exposed to micromolar concentrations of sodium cyanide while neural and synaptic function were monitored in the CA1 region. Cyanide concentrations between 10 and 200 microM rapidly depressed synaptic transmission between Schaffer collateral-commissural fibers and CA1 pyramidal cells. Analysis of input/output curves revealed that the suppression had two components, a decrease in EPSP generation and an increase in action potential threshold. Direct electrical excitability of axons was not affected. At concentrations to 500 microM, cyanide had no effect on antidromic activation of pyramidal cells. At 1000 microM, cyanide caused a moderate depression of the antidromic response in one slice while having no effect in one other. In some experiments, postsynaptic responses in the gyrus dentatus (GD), evoked by perforant path stimulation, were recorded simultaneously with CA1 responses during cyanide application. GD was found to be less sensitive to cyanide than CA1. All cyanide effects reversed rapidly and completely upon washout. These findings suggest that cyanide has a direct effect on neurons not mediated by its inhibition of metabolism.