scholarly journals Selective activation of ganglion cells without axon bundles using epiretinal electrical stimulation

2016 ◽  
Author(s):  
Lauren E. Grosberg ◽  
Karthik Ganesan ◽  
Georges A. Goetz ◽  
Sasidhar Madugula ◽  
Nandita Bhaskar ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Retinal Ganglion Cells ◽  
Large Scale ◽  
Ganglion Cells ◽  
Propagation Speed ◽  
Peripheral Retina ◽  
Retinal Ganglion ◽  
Selective Activation ◽  
Central Retina ◽  
Axon Bundle

AbstractEpiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This paper introduces a method to detect axon bundle activation based on its electrical signature, and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multi-electrode system (512 electrodes, 10 µm diameter, 60 µm pitch). Axon bundle signals were identified by their bi-directional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of all ganglion cells) over the array. In the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses.New & NoteworthyLarge-scale multi-electrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation based on its unique electrical signature, and used to find that a subset of ganglion cells can be activated at single-cell, single-spike resolution without producing bundle activity, in peripheral and central retina. These findings have implications for the development of advanced retinal prostheses.

scholarly journals Activation of ganglion cells and axon bundles using epiretinal electrical stimulation

2017 ◽  
Vol 118 (3) ◽  
pp. 1457-1471 ◽  
Author(s):  
Lauren E. Grosberg ◽  
Karthik Ganesan ◽  
Georges A. Goetz ◽  
Sasidhar S. Madugula ◽  
Nandita Bhaskhar ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Retinal Ganglion Cells ◽  
Large Scale ◽  
Ganglion Cells ◽  
Propagation Speed ◽  
Peripheral Retina ◽  
Retinal Ganglion ◽  
Central Retina ◽  
Axon Bundle ◽  
Stimulation Current

Epiretinal prostheses for treating blindness activate axon bundles, causing large, arc-shaped visual percepts that limit the quality of artificial vision. Improving the function of epiretinal prostheses therefore requires understanding and avoiding axon bundle activation. This study introduces a method to detect axon bundle activation on the basis of its electrical signature and uses the method to test whether epiretinal stimulation can directly elicit spikes in individual retinal ganglion cells without activating nearby axon bundles. Combined electrical stimulation and recording from isolated primate retina were performed using a custom multielectrode system (512 electrodes, 10-μm diameter, 60-μm pitch). Axon bundle signals were identified by their bidirectional propagation, speed, and increasing amplitude as a function of stimulation current. The threshold for bundle activation varied across electrodes and retinas, and was in the same range as the threshold for activating retinal ganglion cells near their somas. In the peripheral retina, 45% of electrodes that activated individual ganglion cells (17% of all electrodes) did so without activating bundles. This permitted selective activation of 21% of recorded ganglion cells (7% of expected ganglion cells) over the array. In one recording in the central retina, 75% of electrodes that activated individual ganglion cells (16% of all electrodes) did so without activating bundles. The ability to selectively activate a subset of retinal ganglion cells without axon bundles suggests a possible novel architecture for future epiretinal prostheses. NEW & NOTEWORTHY Large-scale multielectrode recording and stimulation were used to test how selectively retinal ganglion cells can be electrically activated without activating axon bundles. A novel method was developed to identify axon activation on the basis of its unique electrical signature and was used to find that a subset of ganglion cells can be activated at single-cell, single-spike resolution without producing bundle activity in peripheral and central retina. These findings have implications for the development of advanced retinal prostheses.

scholarly journals Focal Electrical Stimulation of Human Retinal Ganglion Cells

2020 ◽  
Author(s):  
Sasi Madugula ◽  
Alex R. Gogliettino ◽  
Moosa Zaidi ◽  
Gorish Aggarwal ◽  
Alexandra Kling ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Retinal Ganglion Cells ◽  
Visual Information ◽  
Large Scale ◽  
Ganglion Cells ◽  
Cell Types ◽  
Retinal Ganglion ◽  
Single Spike ◽  
Axon Bundle ◽  
Stimulation Of

ABSTRACTElectrical stimulation of retinal ganglion cells (RGCs), which transmit visual information to the brain, is used in retinal implants to treat blindness caused by photoreceptor degeneration. However, the performance of existing clinical implants is limited by indiscriminate stimulation of many cells and cell types. Recent work in isolated macaque retina has shown the ability to precisely evoke spikes in the major RGC types by direct electrical stimulation at safe current levels, with single-cell, single-spike resolution and avoidance of axon bundle activation in many cases. However, these findings have not been verified in the human retina. Here, electrical activation of the major human RGC types was examined using large-scale, multi-electrode recording and stimulation and compared to results from several macaque retinas obtained using the same methods. Electrical stimulation of the major human RGC types closely paralleled results in macaque, with similar somatic and axonal stimulation thresholds, cellular and cell type selectivity of stimulation, avoidance of axon bundle stimulation by calibration, targeting of different cell types based on their distinct electrical signatures, and potential efficacy of real-time stimulus optimization for artificial vision. The results indicate that the macaque retina provides a quantitatively accurate picture of how focal electrical stimulation can be used in future high-resolution implants.

scholarly journals Efficient Inference of Sensitivity to Electrical Stimulation from Intrinsic Electrical Properties of Primate Retinal Ganglion Cells

2021 ◽  
Author(s):  
Sasi S Madugula ◽  
Lauren E Grosberg ◽  
Nishal P Shah ◽  
Alexandra Kling ◽  
Alex R Goglietino ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Electrical Properties ◽  
Retinal Ganglion Cells ◽  
Large Scale ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
High Fidelity ◽  
Retinal Ganglion ◽  
Neural Implants ◽  
Sensory Neural

High-fidelity sensory neural implants must be calibrated to precisely activate specific cells via extracellular stimulation. However, collecting and analyzing the required electrical stimulation data may be difficult in the clinic. A potential solution is to infer stimulation sensitivity from intrinsic electrical properties. Here, this inference was tested using large-scale high-density stimulation and recording from macaque retinal ganglion cells ex vivo. Electrodes recording larger spikes exhibited lower activation thresholds, with distinct trends for somas and axons, and consistent trends across cells and retinas. Thresholds for somatic electrodes increased with distance from the axon initial segment. Responses were inversely related to thresholds, and exhibited a steeper dependence on injected current for axonal than somatic electrodes. Dendritic electrodes were largely ineffective for eliciting spikes. Biophysical simulations qualitatively reproduced these findings. Inference of stimulation sensitivity was employed in simulated visual reconstruction, revealing that the approach could improve the function of future high-fidelity retinal implants.

The development of the pattern of retinal ganglion cells in the chick retina: mechanisms that control differentiation

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5713-5724 ◽  
Author(s):  
K.L. McCabe ◽  
E.C. Gunther ◽  
T.A. Reh
Keyword(s):  
Cell Differentiation ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Receptor Activation ◽  
Peripheral Retina ◽  
Retinal Ganglion ◽  
Fgf Receptor ◽  
Chick Retina ◽  
Regular Arrays

Neurons in both vertebrate and invertebrate eyes are organized in regular arrays. Although much is known about the mechanisms involved in the formation of the regular arrays of neurons found in invertebrate eyes, much less is known about the mechanisms of formation of neuronal mosaics in the vertebrate eye. The purpose of these studies was to determine the cellular mechanisms that pattern the first neurons in vertebrate retina, the retinal ganglion cells. We have found that the ganglion cells in the chick retina develop as a patterned array that spreads from the central to peripheral retina as a wave front of differentiation. The onset of ganglion cell differentiation keeps pace with overall retinal growth; however, there is no clear cell cycle synchronization at the front of differentiation of the first ganglion cells. The differentiation of ganglion cells is not dependent on signals from previously formed ganglion cells, since isolation of the peripheral retina by as much as 400 μm from the front of ganglion cell differentiation does not prevent new ganglion cells from developing. Consistent with previous studies, blocking FGF receptor activation with a specific inhibitor to the FGFRs retards the movement of the front of ganglion cell differentiation, while application of exogenous FGF1 causes the precocious development of ganglion cells in peripheral retina. Our observations, taken together with those of previous studies, support a role for FGFs and FGF receptor activation in the initial development of retinal ganglion cells from the undifferentiated neuroepithelium peripheral to the expanding wave front of differentiation.

Survival-Promoting Effect of Electrical Stimulation on Axotomized Retinal Ganglion Cells

2003 ◽  
pp. 156-159
Author(s):  
Tomomitsu Miyoshi ◽  
Takeshi Morimoto ◽  
Toru Yakura ◽  
Yuka Okazaki ◽  
Takuji Kurimoto ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Promoting Effect

Morphogenesis of retinal ganglion cells during formation of the fovea in the Rhesus macaque

1992 ◽  
Vol 9 (6) ◽  
pp. 603-616 ◽  
Author(s):  
Michael A. Kirby ◽  
Thomas C. Steineke
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Primary Dendrite ◽  
Dendritic Arbor ◽  
Inner Plexiform Layer ◽  
Comparative Neurology ◽  
Retinal Ganglion ◽  
Central Retina ◽  
The Future ◽  
The Mean

AbstractThe morphology of retinal ganglion cells within the central retina during formation of the fovea was examined in retinal explants with horseradish-peroxidase histochemistry. A foveal depression was first apparent in retinal wholemounts at embryonic day 112 (El 12; gestational term is approximately 165 days). At earlier fetal ages, the site of the future fovea was identified by several criteria that included peak density of ganglion cells, lack of blood vessels in the inner retinal layers, arcuate fiber bundles, and the absence of rod outer segments in the photoreceptor layer. Prior to E112, the terminal dendritic arbor of retinal ganglion cells within the central retina extended into the inner plexiform layer and were located directly beneath their somas of origin or at most were slightly displaced from it. For example, at E90 the mean horizontal displacement of the geometric center of the dendritic arbor from the somas of cells within 600 μm of the estimated center of the future fovea was 4.1 μm (S.D. 2.7, range 1.0-10.0, n = 97). Following formation of the foveal depression the dendritic arbors of cells were significantly displaced from their somas. For example, at E138 the mean displacement was 41.2 μm (S.D. 12.2, range 12.0-56.0, n = 97). The displacement of the dendritic arbor which occurred during this period was not accounted for by areal growth of the dendritic arbor, the somas, or the retina, but was produced by the lengthening of the primary dendritic trunk. Moreover, no significant displacement was observed within the remaining 1.5–6.5 mm of the central retina. These observations provide evidence supporting early speculations that the formation of the foveal pit occurs, in part, by the radial migration of ganglion cells from the center of the fovea during its formation. Our analyses suggest that this migration occurs by the lengthening of the primary dendrite presumably by the addition of membrane. This migration is in a direction opposite to the inward movement of photoreceptors that occurs during late fetal and early postnatal periods (Packer et al., 1990, Journal of Comparative Neurology 298, 472–493).

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