Calcium channel dynamics limit synaptic release in response to prosthetic stimulation with sinusoidal waveforms

Freeman, Darren; Jeng, Jed S; Kelly, Shawn K.; Hartveit, Espen; Fried, Shelley I.

doi:10.1088/1741-2560/8/4/046005

Cited by 26 publications

(35 citation statements)

References 68 publications

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“…The only studies to measure spike rates during repetitive stimulation with long-duration waveforms (5–25-Hz sinusoids) did not report any effects of desensitization ( 18, 19 ). A modeling study by the same group predicted that calcium channels, which underlie synaptic release from bipolar cells, respond robustly to repetitive sine-wave stimulation in this frequency range ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Improving the spatial resolution of epiretinal implants by increasing stimulus pulse duration

et al. 2015

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Retinal prosthetic implants are the only approved treatment for retinitis pigmentosa, a disease of the eye that causes blindness through gradual degeneration of photoreceptors. An array of microelectrodes triggered by input from a camera stimulates surviving retinal neurons, each electrode acting as a pixel. Unintended stimulation of retinal ganglion cell axons causes patients to see large, oblong shapes of light, rather than focal spots, making it difficult for them to perceive forms. To address this problem, we performed calcium imaging in isolated retinas and mapped the patterns of cells activated by different electrical stimulation protocols. We found that pulse durations two orders of magnitude longer than those typically used in existing implants stimulate inner retinal neurons while avoiding activation of ganglion cell axons, thus confining retinal responses to the site of the electrode. We show that multielectrode stimulation with 25-ms pulses can pattern letters on the retina corresponding to a Snellen acuity of 20/312. We validated our findings in a patient with an implanted epiretinal prosthesis by demonstrating that 25-ms pulses evoke focal spots of light.

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Section: Discussionmentioning

confidence: 99%

Improving the spatial resolution of epiretinal implants by increasing stimulus pulse duration

et al. 2015

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“…Freemen proposed that the L-type calcium channel in bipolar cells plays a key role in this behavior. [74]…”

Section: Biological Researchmentioning

confidence: 99%

Retinal Prosthesis

Weiland

Humayun

2014

IEEE Trans. Biomed. Eng.

173

123

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Retinal prosthesis have been translated from the laboratory to the clinical over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa. These devices provide partial sight restoration and patients use this improved vision in their everyday lives. Improved mobility and object detection are some of the more notable findings from the clinical trials. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. This paper reviews the recent clinical trials, highlights technology breakthroughs that will contribute to next generation of retinal prostheses.

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“…In contrast to ganglion cells, bipolar cells and photoreceptors do not contain similar densities of sodium channels and as such are less sensitive to transient depolarizations. Instead, these neurons respond to longer duration stimuli, probably because their activation is mediated by ion channels that have longer time constants [ 21 ]. Consistent with these findings, low frequency sinusoidal waveforms were shown to activate the network (bipolar cells and/or photoreceptors) with thresholds that were at least an order of magnitude lower than the thresholds for activating passing axons [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

The Retinal Response to Sinusoidal Electrical Stimulation

Twyford

Fried

2016

IEEE Trans. Neural Syst. Rehabil. Eng.

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Rectangular electrical pulses are the primary stimulus waveform used in retinal prosthetics as well as many other neural stimulation applications. Unfortunately, the utility of pulsatile stimuli is limited by the inability to avoid the activation of passing axons which can result in the distortion of the spatial patterns of elicited neural activity. Because avoiding axons would likely improve clinical outcomes, the examination of alternate stimulus waveforms is warranted. Here, we studied the response of rabbit retinal ganglion cells (RGCs) to sinusoidal electrical stimulation applied at frequencies of 5, 10, 25, and 100 Hz. Targeted RGCs were restricted to 4 common types: OFF-Brisk Transient, OFF-Sustained, ON-Brisk Transient, and ON-Sustained. Interestingly, response patterns varied between different types; the most notable difference was the relatively weak response of ON-Sustained cells to low frequencies. Calculation of total spike counts per trial revealed that lower frequencies are more charge efficient than high frequencies. Finally, experiments utilizing synaptic blockers revealed that 5 and 10 Hz activate photoreceptors while 25 and 100 Hz activate RGCs. Taken together, our results suggest that while sinusoidal electrical stimulation may provide a useful research tool, its clinical utility may be limited.

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Calcium channel dynamics limit synaptic release in response to prosthetic stimulation with sinusoidal waveforms

Cited by 26 publications

References 68 publications

Improving the spatial resolution of epiretinal implants by increasing stimulus pulse duration

Improving the spatial resolution of epiretinal implants by increasing stimulus pulse duration

Retinal Prosthesis

The Retinal Response to Sinusoidal Electrical Stimulation

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