Thresholds for Activation of Rabbit Retinal Ganglion Cells with an Ultrafine, Extracellular Microelectrode

Jensen, Ralph J.; Rizzo, Joseph F.; Ziv, O. R.; Grumet, Andrew; Wyatt, John L.

doi:10.1167/iovs.02-1041

Cited by 144 publications

(159 citation statements)

References 24 publications

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“…Thresholds increased with the square of the distance to the stimulation site, consistent with the inverse square decline of electrical field strength. A similar observation was made for monophasic stimulation of rabbit retinal ganglion cells (Jensen et al, 2003).…”

Section: Somasupporting

confidence: 76%

“…Such stimulation attempts use much larger electrodes (125-500 m) and/or long-duration stimulation pulses (ϳ1 ms), and result in multiple evoked spikes at long latencies (ϳ10 ms). With these stimulation configurations, spike thresholds are typically much higher than the direct-activation values reported in this study (Jensen et al, 2003;Suzuki et al, 2004;Guven et al, 2005;Jensen and Rizzo, 2007;Ye and Goo, 2007). Results from the present study are most comparable with recently published reports of epiretinal stimulation that activated ganglion cells directly by using small electrodes and short pulses: 0.05-0.31 mC/cm 2 for 40 m disk electrodes in frog retina (Kuras et al, 2004), 0.14 -0.25 mC/cm 2 for 30 m cone-shaped electrodes in rabbit retina (Fried et al, 2006), and 0.02-0.20 mC/ cm 2 for 8 -12 m disk electrodes in rat retina (Sekirnjak et al, 2007).…”

Section: Low Stimulation Thresholdscontrasting

confidence: 56%

“…Figure 4 includes several additional cells that were only stimulated directly at the primary electrode. The dashed line is a linear fit to the data and corresponds to an inverse square sensitivity to electrical stimulation (R 2 ϭ 0.58) (Jensen et al, 2003).…”

Section: Dependence Of Thresholds On Stimulus Locationmentioning

confidence: 99%

See 2 more Smart Citations

High-Resolution Electrical Stimulation of Primate Retina for Epiretinal Implant Design

Sekirnjak¹,

Hottowy²,

Sher³

et al. 2008

J. Neurosci.

189

223

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The development of retinal implants for the blind depends crucially on understanding how neurons in the retina respond to electrical stimulation. This study used multielectrode arrays to stimulate ganglion cells in the peripheral macaque retina, which is very similar to the human retina. Analysis was restricted to parasol cells, which form one of the major high-resolution visual pathways in primates. Individual cells were characterized using visual stimuli, and subsequently targeted for electrical stimulation using electrodes 9 -15 m in diameter.

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Section: Somasupporting

confidence: 76%

Section: Low Stimulation Thresholdscontrasting

confidence: 56%

See 1 more Smart Citation

High-Resolution Electrical Stimulation of Primate Retina for Epiretinal Implant Design

Sekirnjak¹,

Hottowy²,

Sher³

et al. 2008

J. Neurosci.

189

223

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show abstract

“…One potential therapy is the development of prosthetic devices to restore lost visual function. Our group ( Figure 1) [2] and others [3][4][5] are engaged in ongoing research to develop a retinal prosthesis that restores vision to patients with degeneration of the outer retina (i.e. the photoreceptors).…”

Section: Introductionmentioning

confidence: 99%

Tissue engineering applied to the retinal prosthesis: Neurotrophin-eluting polymeric hydrogel coatings

Winter

Gokhale

Jensen

et al. 2008

Materials Science and Engineering: C

Self Cite

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Several groups are developing visual prostheses to aid patients with vision loss. While these devices have shown some success in the clinic, they are severely limited by poor resolution, and in many cases have as few as 15 electrodes. Pixel density is poor because high stimulation thresholds require large electrodes to minimize charge density that would otherwise damage the electrode and tissue. A significant contributor to high stimulation threshold requirements is poor biocompatibility. We investigated the application of one system popular in tissue engineering, drug-releasing hydrogels, as a mechanism to improve the tissue-electrode interface. Hydrogels studied (i.e., PEGPLA photocrosslinkable polymers) released neurotrophic factors (i.e., BDNF) known to promote neuron survival and neurite extension in the retina. Hydrogels were examined in co-culture with retinal explants for 7 and 14 days, at which time neurite extension and neurite density was measured. Neurite extension was enhanced in samples exposed to BDNF-releasing hydrogels at 7 days; however, these increases were absent by day 14 suggesting declining drug release. Thus, PEGPLA hydrogels are excellent candidates for short-term (< 14 day) acute release of therapeutic factors in the retina, but will require additional modifications for application with neural prostheses. Additionally, these results suggest that the effects of neurotrophic factors are short-lived in the absence of additional support cues, and tissue engineering systems employing such factors may only produce transient benefits to the patient.

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“…The electrical stimulation of the ex vivo mammalian retina with metal-based electrodes has been extensively studied in both epiretinal (Fried et al 2006;Jensen et al 2003;Sekirnjak et al 2008) and subretinal Rizzo 2006, 2009;Stett et al 2000Stett et al , 2007Tsai et al 2009) configurations. In the epiretinal configuration the stimulation electrode is close to the retinal projection neurons, the ganglion cells, whereas in the subretinal configuration the stimulation electrode is close to the outer retina.…”

mentioning

confidence: 99%

Electrical stimulation of retinal neurons in epiretinal and subretinal configuration using a multicapacitor array

Eickenscheidt

Jenkner

Thewes

et al. 2012

Journal of Neurophysiology

110

120

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Eickenscheidt M, Jenkner M, Thewes R, Fromherz P, Zeck G. Electrical stimulation of retinal neurons in epiretinal and subretinal configuration using a multicapacitor array. J Neurophysiol 107: 2742-2755, 2012. First published February 22, 2012 doi:10.1152/jn.00909.2011.-Electrical stimulation of retinal neurons offers the possibility of partial restoration of visual function. Challenges in neuroprosthetic applications are the long-term stability of the metal-based devices and the physiological activation of retinal circuitry. In this study, we demonstrate electrical stimulation of different classes of retinal neurons with a multicapacitor array. The array-insulated by an inert oxideallows for safe stimulation with monophasic anodal or cathodal current pulses of low amplitude. Ex vivo rabbit retinas were interfaced in either epiretinal or subretinal configuration to the multicapacitor array. The evoked activity was recorded from ganglion cells that respond to light increments by an extracellular tungsten electrode. First, a monophasic epiretinal cathodal or a subretinal anodal current pulse evokes a complex burst of action potentials in ganglion cells. The first action potential occurs within 1 ms and is attributed to direct stimulation. Within the next milliseconds additional spikes are evoked through bipolar cell or photoreceptor depolarization, as confirmed by pharmacological blockers. Second, monophasic epiretinal anodal or subretinal cathodal currents elicit spikes in ganglion cells by hyperpolarization of photoreceptor terminals. These stimuli mimic the photoreceptor response to light increments. Third, the stimulation symmetry between current polarities (anodal/cathodal) and retina-array configuration (epi/sub) is confirmed in an experiment in which stimuli presented at different positions reveal the center-surround organization of the ganglion cell. A simple biophysical model that relies on voltage changes of cell terminals in the transretinal electric field above the stimulation capacitor explains our results. This study provides a comprehensive guide for efficient stimulation of different retinal neuronal classes with low-amplitude capacitive currents.

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Thresholds for Activation of Rabbit Retinal Ganglion Cells with an Ultrafine, Extracellular Microelectrode

Abstract: The results suggest that cathodal stimulation should produce lower thresholds, more localized stimulation, and somewhat better selectivity for cell bodies over axons than would anodal stimulation.

Cited by 144 publications

References 24 publications

High-Resolution Electrical Stimulation of Primate Retina for Epiretinal Implant Design

High-Resolution Electrical Stimulation of Primate Retina for Epiretinal Implant Design

Tissue engineering applied to the retinal prosthesis: Neurotrophin-eluting polymeric hydrogel coatings

Electrical stimulation of retinal neurons in epiretinal and subretinal configuration using a multicapacitor array

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