| Objectives:As the optic nerve can be reached easily, and for most patients with eye diseases (such as retinitis pigmentosa or macular degeneration), there are still a considerable number of live optic nerve, optic nerve was targeted as a potential site for implemention of a visual prosthesis. In order to comprehend the optic nerve prosthesis mechanism, to design a optic nerve prosthesis and instruct the related clinical trial, we need to understand the optic nerve excitability. Oozeer et al proposed an optic nerve model to describe mammalian optic nerve fiber excitability (named as Oozeer optic model). In this paper, the Oozeer optic fiber model was studied and the dynamics characteristics of membranes were analyzed, such as, the role of ion channels during the production process of the action potential. Furthermore, to seek for an effective stimulus waveforms, how the Oozeer optic model responses to different waveform stimulus was explored.Methods:1. Analysis and simulation of Oozeer optic nerve model. Oozeer optic model was used as an object and Matlab as the simulation platform, Euler algorithm was applied to simulate and analyze the mammalian nerve fiber membrane dynamic characteristic.2. Phase plane analysis on dynamic characteristic of membrane. In phase plane,V was used as Abscissa and dV/dt as the vertical axis. The tendency of ion channels during the production process of action potential and the change in the action potential with or without A-current were analyzed.3. Optimization of bipolar rectangular stimulation waveform. By changing the gap between the traditional cathode-anode bipolar rectangular pulses, reversing the sequence of cathode and anode pulse, and inputing these improved pulse to the Oozeer optic nerve model, the traditional bipolar rectangular pulses were optimized. Whether the two improved waveforms could improve the effectiveness in terms of the threshold was investigated.4. The influence of waveform shape on the response of nerve stimulation. Seven waveforms, including Rectangular(Rect), Linear Increase(LinInc),Linear Decrease(LinDec),Exponential Increase(ExpInc),Exponential Decrease(ExpDec), Gaussian(Gauss) and Sinusoidal(Sin), were selected as Oozeer optic model inputs and the responses of membrane potential and the gating variables for each stimulus waveform were analyzed. Phase plane analysis was applied to see the changes of dV/dt to V under different wave stimulations.Results:1. The simulations of membrane dynamic characteristics in Oozeer optic model shows that the ascent stage of action potential was mainly affected by the traditional fast sodium current, and A-type potassium played a major role in the repolarization, while the influence of continuous sodium current and slow potassium current was very small.2. Phase plane analysis of A-type currents shows that model voltage variation with A-type currents was slow, and without A-type currents, the model voltage increased quickly. With A-type currents, repolarization phase occurred when the pulse voltage was20mV, while without A-type currents, it was40mV. Action potential containing A-type currents lasted for about3.9ms and without A-type currents, it was about4.8ms on the V-t graph.3. Simulation of bipolar rectangular stimulation show that the threshold changed from178.3uA/cm2for a cathodic-gap-anodic(CGA) pulse without a gap to170.3uA/cm2for a pulse with0.72ms gap. The threshold was171uAcm2when gap length was0.37ms,where an improvement of more than90%of the maximum possible improvement was already obtained. Anodic-gap-cathodic (AGC) pulse also produced action potential but the threshold was197.3μA/cm2.When the gap length was1.7ms, it showed a lowest threshold of175.6μA/cm2. The threshold was178.3μA/cm2for a pulse with1.2ms gap. At this time, the improvement of87.5%of the maximum possible improvement was already achieved. 4. Simulation of seven stimulus waveforms show that a sluggish response of Explnc and LinInc waveform stimulus was observed, but same response for Rect, Gaussian and Sin waveform was very small. A full scale action potential was finished for ExpDec and LinDec waveform even before the end of pulse.Conclusion:1. The Oozeer optic model membrane dynamics simulation shows that different ion current plays different roles in the formation of action potential. Understanding the ion channels can provide a simulation foundation for designing selective electrical stimulation waveform and controlling the response of nerve fibers.2. A-type potassium current has a special role in action potential formation process. It will not only delay the action potential but also shorten the duration of the action potential, and slow down the rise of membrane potential when the action potential reaches spike threshold.3. Optimization of bipolar stimulation rectangular stimulation waveform showed that both gap between cathodic-gap-anodic phase and their order can enhance the effectiveness of stimulation. Based on change of the threshold to pulse gap length, an optimum gap length can be selected, so that the effectiveness of stimulus could be greatly increased.4. Different stimulus waveform simulation show that there can be other wave waveforms as stimulation inputs in addition to rectangular shape,but responses to different stimuli waveforms are not the same. Changing waveform shapes can provide a method for the selection of effective stimulation, but the existing results still can not determine the optimal stimulation waveform, and further study is needed. |
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