Tickling the retina: integration of subthreshold electrical pulses can activate retinal neurons

Sekhar, Sudarshan; Jalligampala, Archana; Zrenner, Eberhart; Rathbun, Daniel L.

doi:10.1088/1741-2560/13/4/046004

Cited by 37 publications

(85 citation statements)

References 30 publications

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“…Subsequently fit linear-nonlinear models accurately predicted RGC responses to electrical stimulation 38,39 . Linear filters of mouse RGCs could also be recovered with a spatially uniform white noise stimulus consisting of normally distributed subthreshold voltage pulses 40,41 . The results of these studies demonstrate the feasibility of the white noise analysis approach in electrical stimulation.…”

mentioning

confidence: 99%

Probing and predicting ganglion cell responses to smooth electrical stimulation in healthy and blind mouse retina

Höfling

Oesterle

Berens

et al. 2020

Sci Rep

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Retinal implants are used to replace lost photoreceptors in blind patients suffering from retinopathies such as retinitis pigmentosa. Patients wearing implants regain some rudimentary visual function. However, it is severely limited compared to normal vision because non-physiological stimulation strategies fail to selectively activate different retinal pathways at sufficient spatial and temporal resolution. The development of improved stimulation strategies is rendered difficult by the large space of potential stimuli. Here we systematically explore a subspace of potential stimuli by electrically stimulating healthy and blind mouse retina in epiretinal configuration using smooth Gaussian white noise delivered by a high-density CMOS-based microelectrode array. We identify linear filters of retinal ganglion cells (RGCs) by fitting a linear-nonlinear-Poisson (LNP) model. Our stimulus evokes spatially and temporally confined spiking responses in RGC which are accurately predicted by the LNP model. Furthermore, we find diverse shapes of linear filters in the linear stage of the model, suggesting diverse preferred electrical stimuli of RGCs. The linear filter base identified by our approach could provide a starting point of a model-guided search for improved stimuli for retinal prosthetics.

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mentioning

confidence: 99%

Probing and predicting ganglion cell responses to smooth electrical stimulation in healthy and blind mouse retina

Höfling

Oesterle

Berens

et al. 2020

Sci Rep

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“…In an absence of independence (hysteresis), researchers must take careful measures to account for adaptation to electrical stimuli. One method is to deliver ‘probe’ stimuli within the context of ongoing electrical stimulation [23]. An alternate method is to randomize the presentation of pulses, and average repetitions with different preceding stimulation histories [13].…”

Section: Discussionmentioning

confidence: 99%

“…One such elaboration is the use of white-noise mapping which has the advantage that it is easily scalable to recording from tens to hundreds of simultaneously recorded RGCs. Although well-known in the world of visual neurophysiology, such linear systems methods have only recently been applied to visual prosthesis research [23, 25]. As a better understanding of the dozens of different RGC types develops [21], it may become possible to target only RGCs with the smallest eRFs in order to provide the highest-possible prosthetic visual acuity.…”

Section: Discussionmentioning

confidence: 99%

The Spatial Extent of Epiretinal Electrical Stimulation in the Healthy Mouse Retina

et al. 2017

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Background/Aims: Retinal prostheses use electrical stimulation to restore functional vision to patients blinded by retinitis pigmentosa. A key detail is the spatial pattern of ganglion cells activated by stimulation. Therefore, we characterized the spatial extent of network-mediated electrical activation of retinal ganglion cells (RGCs) in the epiretinal monopolar electrode configuration. Methods: Healthy mouse RGC activities were recorded with a micro-electrode array (MEA). The stimuli consisted of monophasic rectangular cathodic voltage pulses and cycling full-field light flashes. Results: Voltage tuning curves exhibited significant hysteresis, reflecting adaptation to electrical stimulation on the time scale of seconds. Responses decreased from 0 to 300 µm, and were also dependent on the strength of stimulation. Applying the Rayleigh criterion to the half-width at half-maximum of the electrical point spread function suggests a visual acuity limit of no better than 20/946. Threshold voltage showed only a modest increase across these distances. Conclusion: The existence of significant hysteresis requires that future investigations of electrical retinal stimulation control for such long-memory adaptation. The spread of electrical activation beyond 200 µm suggests that neighbouring electrodes in epiretinal implants based on indirect stimulation of RGCs may be indiscriminable at interelectrode spacings as large as 400 µm.

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“…They found that the random interpulse intervals could lead to lower adaptation rates than stimulation with constant intervals at frequencies above 50 Hz. In another study, Sekhar et al (2016) analyzed the network mediated responses of RGCs to stimulation at 25 Hz, which would typically induce strong fading. As the retinal neurons could respond to sequences of subthreshold stimulation, they suggested the use of subthreshold sequences to minimize the fading problem.…”

Section: Temporal Resolutionmentioning

confidence: 99%

“…The recent progress in spike triggered analysis for retinal stimulation is summarized in Rathbun et al (2018). Sekhar et al (2016) first reconstructed the temporal electrical receptive fields of RGCs in wild type mice and found that the waveforms were different for ON and OFF cells. After further analysis (Sekhar et al, 2017), they showed the waveforms had different polarities.…”

Section: Selective Activationmentioning

confidence: 99%

Stimulation Strategies for Improving the Resolution of Retinal Prostheses

et al. 2020

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Electrical stimulation using implantable devices with arrays of stimulating electrodes is an emerging therapy for neurological diseases. The performance of these devices depends greatly on their ability to activate populations of neurons with high spatiotemporal resolution. To study electrical stimulation of populations of neurons, retina serves as a useful model because the neural network is arranged in a planar array that is easy to access. Moreover, retinal prostheses are under development to restore vision by replacing the function of damaged light sensitive photoreceptors, which makes retinal research directly relevant for curing blindness. Here we provide a progress review on stimulation strategies developed in recent years to improve the resolution of electrical stimulation in retinal prostheses. We focus on studies performed with explanted retinas, in which electrophysiological techniques are the most advanced. We summarize achievements in improving the spatial and temporal resolution of electrical stimulation of the retina and methods to selectively stimulate neurons with different visual functions. Future directions for retinal prostheses development are also discussed, which could provide insights for other types of neuromodulatory devices in which high-resolution electrical stimulation is required.

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Tickling the retina: integration of subthreshold electrical pulses can activate retinal neurons

Cited by 37 publications

References 30 publications

Probing and predicting ganglion cell responses to smooth electrical stimulation in healthy and blind mouse retina

Probing and predicting ganglion cell responses to smooth electrical stimulation in healthy and blind mouse retina

The Spatial Extent of Epiretinal Electrical Stimulation in the Healthy Mouse Retina

Stimulation Strategies for Improving the Resolution of Retinal Prostheses

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