<i>In vitro</i> assessment of the differences in retinal ganglion cell responses to intra- and extracellular electrical stimulation

Kotsakidis, Rebecca; Meffin, Hamish; Ibbotson, M.; Kameneva, Tatiana

doi:10.1088/1741-2552/aac2f7

Cited by 7 publications

(9 citation statements)

References 27 publications

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“…Recent years have also revealed an interesting observation known as the upper threshold phenomenon ( Figure 4B) in RGC activation, i.e., a drop of response efficacy instead of saturation when stimulus strength exceeds a certain amount. The upper thresholds phenomenon was first observed by Boinagrov et al (2012), and then reported again in several other studies (Barriga-Rivera et al, 2017;Guo et al, 2018;Kotsakidis et al, 2018;Meng et al, 2018). Meng et al (2018) found that 20/21 cells exhibited the upper threshold phenomenon when sufficiently high charge was injected.…”

Section: Recent Progress Electrical Stimulation Of Retinal Neuronsmentioning

confidence: 75%

“…However, Walston et al (2018) observed desensitizing responses in ON bipolar cells at frequencies greater than 6 Hz. The cut-off frequencies of direct responses of RGCs vary among morphological types (Hadjinicolaou et al, 2016), and differed between intracellular and extracellular stimulation (Kotsakidis et al, 2018). One possible mechanism of desensitization in direct responses of RGCs is a lack of sodium channel deinactivation (Tsai et al, 2011).…”

Section: Temporal Resolutionmentioning

confidence: 99%

“…However this may have limited relevance to extracellular stimulation. Kotsakidis et al (2018) examined the optimal range of combinations of current amplitude and frequencies (2-2048 Hz) that preferentially activate ON over OFF RGC population responses (Figures 7A,B), and they found the optimal ranges were very different between intracellular and extracellular stimulation.…”

Section: Selective Activationmentioning

confidence: 99%

“…In addition to the work of Kotsakidis et al (2018), there are several other studies that demonstrated the successful selective activation of ON or OFF RGCs. Similar to that of Kotsakidis et al (2018), some of these studies focused on optimizing the current amplitudes and stimulation frequencies for each cell type. Cai et al (2013) pioneered the work using high frequency (1 kHz) biphasic stimulation.…”

Section: Selective Activationmentioning

confidence: 99%

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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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Section: Recent Progress Electrical Stimulation Of Retinal Neuronsmentioning

confidence: 75%

Section: Temporal Resolutionmentioning

confidence: 99%

Section: Selective Activationmentioning

confidence: 99%

Section: Selective Activationmentioning

confidence: 99%

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Stimulation Strategies for Improving the Resolution of Retinal Prostheses

et al. 2020

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“…As extracellular electrical simulation involves in neuroscience and neural tissue engineering [26][27][28], attention is focused on nanowires applications for visual neural system [29][30][31], brain [32,33] and cardiac [34]. Nanowires have recognized as widely used nanostructure for the cell microenvironment where the electrodynamic properties [35] have permanently affected cellular functions, such as morphology, adhesion, differentiation, and proliferation [36].…”

Section: Introductionmentioning

confidence: 99%

Application of Nanowires for Retinal Regeneration

Kharaghani¹,

Tajbakhsh²,

Phan³

et al. 2020

Regenerative Medicine

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Nanowires aim at developing advanced architectures are gaining popularity for damaged neural systems. The retina with a complicated structure is an essential part of our visual nervous system. Any disorder inside retina could lead to blindness due to irregularity in transferring neural signals to the brain. In recent years, the emergence of nanostructures, as well as nanowires, has provided a viable means for enhancing the regeneration of retinal. Nanowires with the ability to sense light and converting it to the electrical signals simulate the extracellular electrical properties, which are the newest nanostructures for the retinal applications. The different structure of nanowires has been examined in vitro, and several others are undergoing in vivo for vision recovery. Among the structures, core-shell nanowires and functionalized nanowires with gold nanoparticles attract the attention for the regeneration of retinal neural systems. Herein, subsequently provide an introduction to the anatomy of the retina, and retinal disorders, the latest progress in the regeneration of retina and vision using nanowires will be reviewed. Also, the different structures, including core-shell and functionalized nanowires with nanoparticles, will be examined. Eventually, the point of view and perspective of applying nanowire in retinal regeneration will be offered.

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Discrimination of simple objects decoded from the output of retinal ganglion cells upon sinusoidal electrical stimulation

et al. 2021

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Objective. Most neuroprosthetic implants employ pulsatile square-wave electrical stimuli, which are significantly different from physiological inter-neuronal communication. In case of retinal neuroprosthetics, which use a certain type of pulsatile stimuli, reliable object and contrast discrimination by implanted blind patients remained challenging. Here we investigated to what extent simple objects can be discriminated from the output of retinal ganglion cells (RGCs) upon sinusoidal stimulation. Approach. Spatially confined objects were formed by different combinations of 1024 stimulating microelectrodes. The RGC activity in the ex vivo retina of photoreceptor-degenerated mouse, of healthy mouse or of primate was recorded simultaneously using an interleaved recording microelectrode array implemented in a CMOS-based chip. Main results. We report that application of sinusoidal electrical stimuli (40 Hz) in epiretinal configuration instantaneously and reliably modulates the RGC activity in spatially confined areas at low stimulation threshold charge densities (40 nC mm−2). Classification of overlapping but spatially displaced objects (1° separation) was achieved by distinct spiking activity of selected RGCs. A classifier (regularized logistic regression) discriminated spatially displaced objects (size: 5.5° or 3.5°) with high accuracy (90% or 62%). Stimulation with low artificial contrast (10%) encoded by different stimulus amplitudes generated RGC activity, which was classified with an accuracy of 80% for large objects (5.5°). Significance. We conclude that time-continuous smooth-wave stimulation provides robust, localized neuronal activation in photoreceptor-degenerated retina, which may enable future artificial vision at high temporal, spatial and contrast resolution.

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In vitro assessment of the differences in retinal ganglion cell responses to intra- and extracellular electrical stimulation

Abstract: There is no direct translation of the results obtained with intracellular stimulation to those that employ extracellular stimulation.

Cited by 7 publications

References 27 publications

Stimulation Strategies for Improving the Resolution of Retinal Prostheses

Stimulation Strategies for Improving the Resolution of Retinal Prostheses

Application of Nanowires for Retinal Regeneration

Discrimination of simple objects decoded from the output of retinal ganglion cells upon sinusoidal electrical stimulation

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