scholarly journals Insights from Computational Modelling: Selective Stimulation of Retinal Ganglion Cells

2020 ◽  
pp. 233-247
Author(s):  
Tianruo Guo ◽  
David Tsai ◽  
Siwei Bai ◽  
Mohit Shivdasani ◽  
Madhuvanthi Muralidharan ◽  
...  
Keyword(s):  
Retinal Ganglion Cells ◽  
Computational Models ◽  
Ganglion Cells ◽  
Computational Modelling ◽  
Retinal Ganglion ◽  
Retinal Prostheses ◽  
Differential Activation ◽  
Photoreceptor Layer ◽  
Suprachoroidal Space ◽  
Wide Range

AbstractImprovements to the efficacy of retinal neuroprostheses can be achieved by developing more sophisticated neural stimulation strategies to enable selective or differential activation of specific retinal ganglion cells (RGCs). Recent retinal studies have demonstrated the ability to differentially recruit ON and OFF RGCs – the two major information pathways of the retina – using high-frequency electrical stimulation (HFS). However, there remain many unknowns, since this is a relatively unexplored field. For example, can we achieve ON/OFF selectivity over a wide range of stimulus frequencies and amplitudes? Furthermore, existing demonstrations of HFS efficacy in retinal prostheses have been based on epiretinal placement of electrodes. Other clinically popular techniques include subretinal or suprachoroidal placement, where electrodes are located at the photoreceptor layer or in the suprachoroidal space, respectively, and these locations are quite distant from the RGC layer. Would HFS-based differential activation work from these locations? In this chapter, we conducted in silico investigations to explore the generalizability of HFS to differentially active ON and OFF RGCs. Computational models are particularly well suited for these investigations. The electric field can be accurately described by mathematical formulations, and simulated neurons can be “probed” at resolutions well beyond those achievable by today’s state-of-the-art experimental techniques.

scholarly journals Computational modelling of salamander retinal ganglion cells using machine learning approaches

2019 ◽  
Vol 325 ◽  
pp. 101-112 ◽  
Author(s):  
Gautham P. Das ◽  
Philip J. Vance ◽  
Dermot Kerr ◽  
Sonya A. Coleman ◽  
Thomas M. McGinnity ◽  
...  
Keyword(s):  
Machine Learning ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Computational Modelling ◽  
Learning Approaches ◽  
Retinal Ganglion

Direct Activation and Temporal Response Properties of Rabbit Retinal Ganglion Cells Following Subretinal Stimulation

2009 ◽  
Vol 102 (5) ◽  
pp. 2982-2993 ◽  
Author(s):  
David Tsai ◽  
John W. Morley ◽  
Gregg J. Suaning ◽  
Nigel H. Lovell
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Pigment Epithelium ◽  
Subretinal Space ◽  
High Frequency Stimulation ◽  
Retinal Ganglion ◽  
Photoreceptor Layer ◽  
Direct Activation ◽  
Frequency Stimulation ◽  
Safety Considerations

In the last decade several groups have been developing vision prostheses to restore visual perception to the profoundly blind. Despite some promising results from human trials, further understanding of the neural mechanisms involved is crucial for improving the efficacy of these devices. One of the techniques involves placing stimulating electrodes in the subretinal space between the photoreceptor layer and the pigment epithelium to evoke neural responses in the degenerative retina. This study used cell-attached and whole cell current-clamp recordings to investigate the responses of rabbit retinal ganglion cells (RGCs) following subretinal stimulation with 25-μm-diameter electrodes. We found that direct RGC responses with short latency (≤2 ms using 0.1-ms pulses) could be reliably elicited. The thresholds for these responses were reported for on, off, and on–off RGCs over pulse widths 0.1–5.0 ms. During repetitive stimulation these direct activation responses were more readily elicited than responses arising from stimulation of the retinal network. The temporal spiking characteristics of RGCs were characterized as a function of stimulus configurations. We found that the response profiles could be generalized into four classes with distinctive properties. Our results suggest that for subretinal vision prostheses short pulses are preferable for efficacy and safety considerations, and that direct activation of RGCs will be necessary for reliable activation during high-frequency stimulation.

Activation and inhibition of retinal ganglion cells in response to epiretinal electrical stimulation: a computational modelling study

2014 ◽  
Vol 12 (1) ◽  
pp. 016002 ◽  
Author(s):  
Miganoosh Abramian ◽  
Nigel H Lovell ◽  
John W Morley ◽  
Gregg J Suaning ◽  
Socrates Dokos
Keyword(s):  
Electrical Stimulation ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Computational Modelling ◽  
Retinal Ganglion ◽  
Modelling Study

The Curved Grid Non-Illusions

2017 ◽  
Author(s):  
János Geier ◽  
Mariann Hudák
Keyword(s):  
Statistical Analysis ◽  
Retinal Ganglion Cells ◽  
Line Width ◽  
Ganglion Cells ◽  
Receptive Fields ◽  
Retinal Ganglion ◽  
Illusory Effect ◽  
Grid Line ◽  
Wide Range ◽  
Hermann Grid Illusion

The generally accepted explanation of the Hermann grid illusion is Baumgartner’s hypothesis that the illusory effect is generated by the response of retinal ganglion cells with concentric ON-OFF or OFF-ON receptive fields. To challenge this explanation, some simple distortions to the grid lines were introduced that make the illusion disappear totally, while all preconditions of Baumgartner’s hypothesis remained unchanged. Psychophysical experiments in which the distortion tolerance was measured showed the level of distortion at which the illusion disappears at a given type of distortion for a given subject. Statistical analysis shows that the distortion tolerance is independent of grid-line width within a wide range and of the type of distortion, except when one side of each line remains straight. The conclusion is the main cause of the Hermann grid illusion is the straightness of the edges of the grid lines. Similar results have been obtained in the scintillating grid.

Complex Spike-Event Pattern of Transient on-off Retinal Ganglion Cells

2006 ◽  
Vol 96 (6) ◽  
pp. 2845-2856 ◽  
Author(s):  
Martin Greschner ◽  
Andreas Thiel ◽  
Jutta Kretzberg ◽  
Josef Ammermüller
Keyword(s):  
Retinal Ganglion Cells ◽  
Computational Models ◽  
Ganglion Cells ◽  
Temporal Structure ◽  
Gain Control ◽  
Saccadic Eye Movements ◽  
Cell Subpopulation ◽  
Retinal Ganglion ◽  
Filter Model ◽  
Spike Event

on-off transient ganglion cells of the turtle retina show distinct spike-event patterns in response to abrupt intensity changes, such as during saccadic eye movements. These patterns consist of two main spike events, with the latency of each event showing a systematic dependency on stimulus contrast. Whereas the latency of the first event decreases monotonically with increasing contrast, as expected, the second event shows the shortest latency for intermediate contrasts and a longer latency for high and low contrasts. These spike-event patterns improve the discrimination of different light-intensity transitions based on ensemble responses of the on-off transient ganglion cell subpopulation. Although the discrimination results are far better than chance using either spike counts or latencies of the first spikes, they are further improved by using properties of the second spike event. The best classification results are obtained when spike rates and latencies of both events are considered in combination. Thus spike counts and temporal structure of retinal ganglion cells carry complementary information about the stimulus condition, and thus spike-event patterns could be an important aspect of retinal coding. To investigate the origin of the spike-event patterns in retinal ganglion cells, two computational models of retinal processing are compared. A linear–nonlinear model consisting of separate filters for on and off response components fails to reproduce the spike-event patterns. A more complex cascade filter model, however, accurately predicts the timing of the spike events by using a combination of gain control loop and spike rate adaptation.

scholarly journals Two Metabotropic γ-Aminobutyric Acid Receptors Differentially Modulate Calcium Currents in Retinal Ganglion Cells

1997 ◽  
Vol 110 (1) ◽  
pp. 45-58 ◽  
Author(s):  
Jian Zhang ◽  
Wen Shen ◽  
Malcolm M. Slaughter
Keyword(s):  
Retinal Ganglion Cells ◽  
Gaba Receptors ◽  
Gaba Receptor ◽  
Ganglion Cells ◽  
Calcium Currents ◽  
Gabab Receptors ◽  
Aminobutyric Acid ◽  
Retinal Ganglion ◽  
Wide Range ◽  
Prepulse Facilitation

Metabotropic γ-aminobutyric acid (GABA) receptors were studied in amphibian retinal ganglion cells using whole cell current and voltage clamp techniques. The aim was to identify the types of receptor present and their mechanisms of action and modulation. Previous results indicated that ganglion cells possess two ionotropic GABA receptors: GABAAR and GABACR. This study demonstrates that they also possess two types of metabotropic GABAB receptor: one sensitive to baclofen and another to cis-aminocrotonic acid (CACA). The effects of these selective agonists were blocked by GDP-β-S. Baclofen suppressed an ω-conotoxin–GVIA-sensitive barium current, and this action was reversed by prepulse facilitation, indicative of a direct G-protein pathway. The effect of baclofen was also partially occluded by agents that influence the protein kinase A (PKA) pathway. But the effect of PKA activation was unaffected by prepulse facilitation, indicating PKA acted through a parallel pathway. Calmodulin antagonists reduced the action of baclofen, whereas inhibitors of calmodulin phosphatase enhanced it. Antagonists of internal calcium release, such as heparin and ruthenium red, did not affect the baclofen response. Thus, the baclofen-sensitive receptor may respond to influx of calcium. The CACA-sensitive GABA receptor reduced current through dihydropyridine-sensitive channels. Sodium nitroprusside and 8-bromo-cGMP enhanced the action of CACA, indicating that a nitric oxide system can up-regulate this receptor pathway. CACA-sensitive and baclofen-sensitive GABAB receptors reduced spike activity in ganglion cells. Overall, retinal ganglion cells possess four types of GABA receptor, two ionotropic and two metabotropic. Each has a unique electrogenic profile, providing a wide range of neural integration at the final stage of retinal information processing.

scholarly journals The Olivary Pretectal Nucleus Receives Visual Input of High Spatial Resolution

2020 ◽  
Author(s):  
Jared N. Levine ◽  
Gregory W. Schwartz
Keyword(s):  
Single Cell ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Light Level ◽  
Single Type ◽  
Retinal Ganglion ◽  
Retinal Input ◽  
Wide Range ◽  
Pretectal Nucleus ◽  
Single Cell Type

AbstractIn the mouse, retinal output is computed by over 40 distinct types of retinal ganglion cells (RGCs) (Baden et al., 2016). Determining which of these many RGC types project to a retinorecipient region is a key step in elucidating the role that region plays in visually-mediated behaviors. Combining retrograde viral tracing and single-cell electrophysiology, we identify the RGC types which project to the olivary pretectal nucleus (OPN), a major visual structure. We find that retinal input to the OPN consists of a variety of intrinsically-photosensitive and conventional RGC types, the latter a diverse set of mostly ON RGCs. Surprisingly, while the OPN is most associated with the pupillary light reflex (PLR) pathway, requiring information about absolute luminance, we show that the majority of the retinal input to the OPN is from single cell type which transmits information unrelated to luminance. This ON-transient RGC accounts for two-thirds of the input to the OPN, and responds to small objects across a wide range of speeds. This finding suggests a role for the OPN in visually-mediated behaviors beyond the PLR.Significance statementThe olivary pretectal nucleus is a midbrain structure which receives direct input from retinal ganglion cells (RGC), and modulates pupil diameter in response to changing absolute light level. In the present study, we combine viral tracing and electrophysiology to identify the RGC types which project to the OPN. Surprisingly, the majority of its input comes from a single type which does not encode absolute luminance, but instead responds to small objects across a wide range of speeds. These findings are consistent with a role for the OPN apart from pupil control and suggest future experiments to elucidate its full role in visually-mediated behavior.

Insights from computational modelling: Characterising Midget and Parasol Retinal Ganglion Cells using Electrical Stimulation

2021 ◽  
Author(s):  
Xiaoyu Song ◽  
Donglin Wu ◽  
Shirong Qiu ◽  
Zhengyang Liu ◽  
Feng Zhou ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Computational Modelling ◽  
Retinal Ganglion

Calcium-Activated Potassium Conductances in Retinal Ganglion Cells of the Ferret

1998 ◽  
Vol 79 (1) ◽  
pp. 151-158 ◽  
Author(s):  
Guo-Yong Wang ◽  
David W. Robinson ◽  
Leo M. Chalupa
Keyword(s):  
Potassium Channels ◽  
Potassium Channel ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Membrane Properties ◽  
Retinal Ganglion ◽  
Wide Range ◽  
Potassium Conductances ◽  
Calcium Activated Potassium Channels ◽  
Calcium Activated Potassium Channel

Wang, Guo-Yong, David W. Robinson, and Leo M. Chalupa. Calcium-activated potassium conductances in retinal ganglion cells of the ferret. J. Neurophysiol. 79: 151–158, 1998. Patch-clamp recordings were made from isolated and intact retinal ganglion cells (RGCs) of the ferret to examine the calcium-activated potassium channels expressed by these neurons and to determine their functional role in the generation of spikes and spiking patterns. Single-channel recordings from isolated neurons revealed the presence of two calcium-sensitive potassium channels that had conductances of 118 and 22 pS. The properties of these two channels were shown to be similar to those ascribed to the large-conductance calcium-activated potassium channel (BKCa) and small-conductance calcium-activated potassium channel (SKCa) channels in other neurons. Whole cell recordings from isolated RGCs showed that apamin and charybdotoxin (CTX), specific blockers of the SKCa and BKCa channels, respectively, resulted in a shortening of the time to threshold and a reduction in the hyperpolarization after the spike. Addition of these blockers also resulted in a significant increase in spike frequency over a wide range of maintained depolarizations. Similar effects of apamin and CTX were observed during current-clamp recordings from intact alpha and beta ganglion cells, morphologically identified after Lucifer yellow filling. About 20% of these neurons did not exhibit a sensitivity to either blocker, suggesting the presence of functionally distinct subgroups of alpha and beta RGCs on the basis of their intrinsic membrane properties. The expression of these calcium-activated potassium channels in the majority of alpha and beta cells provides a means by which the activity of these output neurons could be modulated by retinal neurochemicals.

Neurolight: A Deep Learning Neural Interface for Cortical Visual Prostheses

2020 ◽  
Vol 30 (09) ◽  
pp. 2050045 ◽  
Author(s):  
Antonio Lozano ◽  
Juan Sebastián Suárez ◽  
Cristina Soto-Sánchez ◽  
Javier Garrigós ◽  
J. Javier Martínez-Alvarez ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Deep Learning ◽  
Retinal Ganglion Cells ◽  
Computational Models ◽  
Microelectrode Array ◽  
Ganglion Cells ◽  
Semantic Segmentation ◽  
Video Stream ◽  
Retinal Ganglion ◽  
Task Oriented

Visual neuroprosthesis, that provide electrical stimulation along several sites of the human visual system, constitute a potential tool for vision restoration for the blind. Scientific and technological progress in the fields of neural engineering and artificial vision comes with new theories and tools that, along with the dawn of modern artificial intelligence, constitute a promising framework for the further development of neurotechnology. In the framework of the development of a Cortical Visual Neuroprosthesis for the blind (CORTIVIS), we are now facing the challenge of developing not only computationally powerful tools and flexible approaches that will allow us to provide some degree of functional vision to individuals who are profoundly blind. In this work, we propose a general neuroprosthesis framework composed of several task-oriented and visual encoding modules. We address the development and implementation of computational models of the firing rates of retinal ganglion cells and design a tool — Neurolight — that allows these models to be interfaced with intracortical microelectrodes in order to create electrical stimulation patterns that can evoke useful perceptions. In addition, the developed framework allows the deployment of a diverse array of state-of-the-art deep-learning techniques for task-oriented and general image pre-processing, such as semantic segmentation and object detection in our system’s pipeline. To the best of our knowledge, this constitutes the first deep-learning-based system designed to directly interface with the visual brain through an intracortical microelectrode array. We implement the complete pipeline, from obtaining a video stream to developing and deploying task-oriented deep-learning models and predictive models of retinal ganglion cells’ encoding of visual inputs under the control of a neurostimulation device able to send electrical train pulses to a microelectrode array implanted at the visual cortex.

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