gms | German Medical Science

Purpose: We are studying the response of retinal neurons to electric stimulation in order to develop more effective methods of stimulation for use during clinical trials. Our recent study indicates 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. We also showed that the property of the sodium channel band varies across types, suggesting that the response to stimulation will be different in each type as well. Here, we are studying which properties of the induced electric field across the band are most important for generating activity.

Methods: We measured the spatial profile of voltage elicited in response to 0.2 ms cathodic pulses from a conical platinum-iridium electrode (100 kΩ 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 voltage 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 profile 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.

Results: 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 properties of the band (e.g. length, distance from the soma).

Conclusions: Our results indicate that we can predict the relative effectiveness of different stimulus configurations for eliciting spiking in retinal ganglion cells. This may help to reduce thresholds for eliciting clinical responses. Also, because the optimum profile was different for different types of ganglion cells, our findings suggest 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.