Effects of high-rate electrical stimulation upon firing in modelled and real neurons.

Many medical devices use high-rate, low-amplitude currents to affect neural function. This study examined the effect of stimulation rate upon action potential threshold and sustained firing rate for two model neurons, the rabbit myelinated fibre and the unmyelinated leech touch sensory cell. These model neurons were constructed with the NEURON simulator from electrophysiological data. Alternating-phase current pulses (0-1250 Hz), of fixed phase duration (0.2 ms), were used to stimulate the neurons, and propagation success or failure was measured. One effect of the high pulse rates was to cause a net depolarisation, and this was verified by the relief of action potential conduction block by 500 Hz extracellular stimulation in leech neurons. The models also predicted that the neurons would maintain maximum sustained firing at a number of different stimulation rates. For example, at twice threshold, the myelinated model followed the stimulus up to 500 Hz stimulation, half the stimulus rate up to 850 Hz stimulation, and it did not fire at 1250 Hz stimulation. By contrast, the unmyelinated neuron model had a lower maximum firing rate of 190 Hz, and this rate was obtained at a number of stimulation rates, up to 1250 Hz. The myelinated model also predicted sustained firing with 1240 Hz stimulation at threshold current, but no firing when the current level was doubled. Most of these effects are explained by the interaction of stimulus pulses with the cell's refractory period.