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S. I. Fried, N. J. Desai, D. K. Eddington, J. F. Rizzo, III; The Distribution of Voltage Across the Proximal Axon Underlies Spike Initiation in Response to Electric Stimulation of Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4568.
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In order to improve the clinical responses associated with retinal prosthetics, we are studying how electric stimulation activates retinal neurons. A recent study indicated that a dense band of sodium channels in the proximal portion of the axon was the site at which activation thresholds were lowest, suggesting that this is also the site of spike initiation. Here, we are studying which properties of the induced electric field across this region are most important for generating activity.
We measured the spatial profile of voltage elicited in response to 0.1 ms cathodic pulses from a conical platinum-iridium electrode (100 k-Ohm impedance). Then we moved the stimulating electrode to multiple sites around the ganglion cell and determined the threshold required to elicit an action potential at each location. Knowledge of the profile allowed us to determine the voltage across the sodium channel band for each location of the stimulating electrode. From this, we could compare the voltage across the band (the spike initiation site) for all ‘successful’ pulses. This allowed us to look for common feature(s) in pulses that activate spiking. We similarly compared the first and second derivatives of the voltage profile across the band as well.
The magnitude of the second derivative across the band was the determining factor as to whether a given pulse would elicit a spike. In other words, if the second derivative of the voltage profile across the band exceeded a certain value, the cell was likely to generate an action potential. The absolute magnitude was different for different types of ganglion cells and was influenced by other properties of the cell as well (i.e. the size of the soma).
Our results suggest that we can gauge the effectiveness of different stimulus configurations for eliciting spiking in retinal ganglion cells. This may help to reduce thresholds for eliciting clinical responses. The optimum profile was different for different types of ganglion cells suggesting that methods to selectively activate individual types may be achievable. This would allow complex patterns of neural activity to be generated and likely result in improved clinical outcomes.
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