Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 8 de 8
Filter
Add more filters










Database
Language
Publication year range
1.
bioRxiv ; 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-37986895

ABSTRACT

Identifying neuronal cell types and their biophysical properties based on their extracellular electrical features is a major challenge for experimental neuroscience and the development of high-resolution brain-machine interfaces. One example is identification of retinal ganglion cell (RGC) types and their visual response properties, which is fundamental for developing future electronic implants that can restore vision. The electrical image (EI) of a RGC, or the mean spatio-temporal voltage footprint of its recorded spikes on a high-density electrode array, contains substantial information about its anatomical, morphological, and functional properties. However, the analysis of these properties is complex because of the high-dimensional nature of the EI. We present a novel optimization-based algorithm to decompose electrical image into a low-dimensional, biophysically-based representation: the temporally-shifted superposition of three learned basis waveforms corresponding to spike waveforms produced in the somatic, dendritic and axonal cellular compartments. Large-scale multi-electrode recordings from the macaque retina were used to test the effectiveness of the decomposition. The decomposition accurately localized the somatic and dendritic compartments of the cell. The imputed dendritic fields of RGCs correctly predicted the location and shape of their visual receptive fields. The inferred waveform amplitudes and shapes accurately identified the four major primate RGC types (ON and OFF midget and parasol cells), a substantial advance. Together, these findings may contribute to more accurate inference of RGC types and their original light responses in the degenerated retina, with possible implications for other electrical imaging applications.

2.
J Neural Eng ; 20(4)2023 08 31.
Article in English | MEDLINE | ID: mdl-37433293

ABSTRACT

Objective. Retinal implants are designed to stimulate retinal ganglion cells (RGCs) in a way that restores sight to individuals blinded by photoreceptor degeneration. Reproducing high-acuity vision with these devices will likely require inferring the natural light responses of diverse RGC types in the implanted retina, without being able to measure them directly. Here we demonstrate an inference approach that exploits intrinsic electrophysiological features of primate RGCs.Approach.First, ON-parasol and OFF-parasol RGC types were identified using their intrinsic electrical features in large-scale multi-electrode recordings from macaque retina. Then, the electrically inferred somatic location, inferred cell type, and average linear-nonlinear-Poisson model parameters of each cell type were used to infer a light response model for each cell. The accuracy of the cell type classification and of reproducing measured light responses with the model were evaluated.Main results.A cell-type classifier trained on 246 large-scale multi-electrode recordings from 148 retinas achieved 95% mean accuracy on 29 test retinas. In five retinas tested, the inferred models achieved an average correlation with measured firing rates of 0.49 for white noise visual stimuli and 0.50 for natural scenes stimuli, compared to 0.65 and 0.58 respectively for models fitted to recorded light responses (an upper bound). Linear decoding of natural images from predicted RGC activity in one retina showed a mean correlation of 0.55 between decoded and true images, compared to an upper bound of 0.81 using models fitted to light response data.Significance.These results suggest that inference of RGC light response properties from intrinsic features of their electrical activity may be a useful approach for high-fidelity sight restoration. The overall strategy of first inferring cell type from electrical features and then exploiting cell type to help infer natural cell function may also prove broadly useful to neural interfaces.


Subject(s)
Retinal Degeneration , Retinal Ganglion Cells , Animals , Retinal Ganglion Cells/physiology , Action Potentials/physiology , Electric Stimulation/methods , Retina/physiology , Macaca
3.
J Neurosci ; 43(26): 4808-4820, 2023 06 28.
Article in English | MEDLINE | ID: mdl-37268418

ABSTRACT

High-fidelity electronic implants can in principle restore the function of neural circuits by precisely activating neurons via extracellular stimulation. However, direct characterization of the individual electrical sensitivity of a large population of target neurons, to precisely control their activity, can be difficult or impossible. A potential solution is to leverage biophysical principles to infer sensitivity to electrical stimulation from features of spontaneous electrical activity, which can be recorded relatively easily. Here, this approach is developed and its potential value for vision restoration is tested quantitatively using large-scale multielectrode stimulation and recording from retinal ganglion cells (RGCs) of male and female macaque monkeys ex vivo Electrodes recording larger spikes from a given cell exhibited lower stimulation thresholds across cell types, retinas, and eccentricities, with systematic and distinct trends for somas and axons. Thresholds for somatic stimulation increased with distance from the axon initial segment. The dependence of spike probability on injected current was inversely related to threshold, and was substantially steeper for axonal than somatic compartments, which could be identified by their recorded electrical signatures. Dendritic stimulation was largely ineffective for eliciting spikes. These trends were quantitatively reproduced with biophysical simulations. Results from human RGCs were broadly similar. The inference of stimulation sensitivity from recorded electrical features was tested in a data-driven simulation of visual reconstruction, revealing that the approach could significantly improve the function of future high-fidelity retinal implants.SIGNIFICANCE STATEMENT This study demonstrates that individual in situ primate retinal ganglion cells of different types respond to artificially generated, external electrical fields in a systematic manner, in accordance with theoretical predictions, that allows for prediction of electrical stimulus sensitivity from recorded spontaneous activity. It also provides evidence that such an approach could be immensely helpful in the calibration of clinical retinal implants.


Subject(s)
Retina , Retinal Ganglion Cells , Animals , Male , Female , Humans , Retinal Ganglion Cells/physiology , Action Potentials/physiology , Retina/physiology , Primates , Electric Stimulation/methods
4.
J Neurosci ; 43(25): 4625-4641, 2023 06 21.
Article in English | MEDLINE | ID: mdl-37188516

ABSTRACT

Electrical stimulation of retinal ganglion cells (RGCs) with electronic implants provides rudimentary artificial vision to people blinded by retinal degeneration. However, current devices stimulate indiscriminately and therefore cannot reproduce the intricate neural code of the retina. Recent work has demonstrated more precise activation of RGCs using focal electrical stimulation with multielectrode arrays in the peripheral macaque retina, but it is unclear how effective this can be in the central retina, which is required for high-resolution vision. This work probes the neural code and effectiveness of focal epiretinal stimulation in the central macaque retina, using large-scale electrical recording and stimulation ex vivo The functional organization, light response properties, and electrical properties of the major RGC types in the central retina were mostly similar to the peripheral retina, with some notable differences in density, kinetics, linearity, spiking statistics, and correlations. The major RGC types could be distinguished by their intrinsic electrical properties. Electrical stimulation targeting parasol cells revealed similar activation thresholds and reduced axon bundle activation in the central retina, but lower stimulation selectivity. Quantitative evaluation of the potential for image reconstruction from electrically evoked parasol cell signals revealed higher overall expected image quality in the central retina. An exploration of inadvertent midget cell activation suggested that it could contribute high spatial frequency noise to the visual signal carried by parasol cells. These results support the possibility of reproducing high-acuity visual signals in the central retina with an epiretinal implant.SIGNIFICANCE STATEMENT Artificial restoration of vision with retinal implants is a major treatment for blindness. However, present-day implants do not provide high-resolution visual perception, in part because they do not reproduce the natural neural code of the retina. Here, we demonstrate the level of visual signal reproduction that is possible with a future implant by examining how accurately responses to electrical stimulation of parasol retinal ganglion cells can convey visual signals. Although the precision of electrical stimulation in the central retina was diminished relative to the peripheral retina, the quality of expected visual signal reconstruction in parasol cells was greater. These findings suggest that visual signals could be restored with high fidelity in the central retina using a future retinal implant.


Subject(s)
Retina , Visual Prosthesis , Animals , Retina/physiology , Retinal Ganglion Cells/physiology , Macaca , Prostheses and Implants , Electric Stimulation/methods , Photic Stimulation/methods
5.
J Neural Eng ; 19(6)2022 12 19.
Article in English | MEDLINE | ID: mdl-36533865

ABSTRACT

Objective. Vision restoration with retinal implants is limited by indiscriminate simultaneous activation of many cells and cell types, which is incompatible with reproducing the neural code of the retina. Recent work has shown that primate retinal ganglion cells (RGCs), which transmit visual information to the brain, can be directly electrically activated with single-cell, single-spike, cell-type precision - however, this possibility has never been tested in the human retina. In this study we aim to characterize, for the first time, direct in situ extracellular electrical stimulation of individual human RGCs.Approach. Extracellular electrical stimulation of individual human RGCs was conducted in three human retinas ex vivo using a custom large-scale, multi-electrode array capable of simultaneous recording and stimulation. Measured activation properties were compared directly to extensive results from macaque.Main results. Precise activation was in many cases possible without activating overlying axon bundles, at low stimulation current levels similar to those used in macaque. The major RGC types could be identified and targeted based on their distinctive electrical signatures. The measured electrical activation properties of RGCs, combined with a dynamic stimulation algorithm, was sufficient to produce an evoked visual signal that was nearly optimal given the constraints of the interface.Significance. These results suggest the possibility of high-fidelity vision restoration in humans using bi-directional epiretinal implants.


Subject(s)
Retinal Ganglion Cells , Visual Prosthesis , Animals , Humans , Retinal Ganglion Cells/physiology , Electric Stimulation/methods , Retina/physiology , Electrodes , Macaca , Action Potentials/physiology , Photic Stimulation/methods
6.
J Neural Eng ; 18(6)2021 11 15.
Article in English | MEDLINE | ID: mdl-34710857

ABSTRACT

Objective.Epiretinal prostheses are designed to restore vision to people blinded by photoreceptor degenerative diseases by stimulating surviving retinal ganglion cells (RGCs), which carry visual signals to the brain. However, inadvertent stimulation of RGCs at their axons can result in non-focal visual percepts, limiting the quality of artificial vision. Theoretical work has suggested that axon activation can be avoided with current stimulation designed to minimize the second spatial derivative of the induced extracellular voltage along the axon. However, this approach has not been verified experimentally at the resolution of single cells.Approach.In this work, a custom multi-electrode array (512 electrodes, 10µm diameter, 60µm pitch) was used to stimulate and record RGCs in macaque retinaex vivoat single-cell, single-spike resolution. RGC activation thresholds resulting from bi-electrode stimulation, which consisted of bipolar currents simultaneously delivered through two electrodes straddling an axon, were compared to activation thresholds from traditional single-electrode stimulation.Main results.On average, across three retinal preparations, the bi-electrode stimulation strategy reduced somatic activation thresholds (∼21%) while increasing axonal activation thresholds (∼14%), thus favoring selective somatic activation. Furthermore, individual examples revealed rescued selective activation of somas that was not possible with any individual electrode.Significance.This work suggests that a bi-electrode epiretinal stimulation strategy can reduce inadvertent axonal activation at cellular resolution, for high-fidelity artificial vision.


Subject(s)
Retinal Ganglion Cells , Visual Prosthesis , Action Potentials/physiology , Axons/physiology , Electric Stimulation , Electrodes , Humans , Retina/physiology , Retinal Ganglion Cells/physiology
7.
J Neural Eng ; 16(2): 025001, 2019 04.
Article in English | MEDLINE | ID: mdl-30523958

ABSTRACT

OBJECTIVE: Epiretinal prostheses are designed to restore vision in people blinded by photoreceptor degenerative diseases, by directly activating retinal ganglion cells (RGCs) using an electrode array implanted on the retina. In present-day clinical devices, current spread from the stimulating electrode to a distant return electrode often results in the activation of many cells, potentially limiting the quality of artificial vision. In the laboratory, epiretinal activation of RGCs with cellular resolution has been demonstrated with small electrodes, but distant returns may still cause undesirable current spread. Here, the ability of local return stimulation to improve the selective activation of RGCs at cellular resolution was evaluated. APPROACH: A custom multi-electrode array (512 electrodes, 10 µm diameter, 60 µm pitch) was used to simultaneously stimulate and record from RGCs in isolated primate retina. Stimulation near the RGC soma with a single electrode and a distant return was compared to stimulation in which the return was provided by six neighboring electrodes. MAIN RESULTS: Local return stimulation enhanced the capability to activate cells near the central electrode (<30 µm) while avoiding cells farther away (>30 µm). This resulted in an improved ability to selectively activate ON and OFF cells, including cells encoding immediately adjacent regions in the visual field. SIGNIFICANCE: These results suggest that a device that restricts the electric field through local returns could optimize activation of neurons at cellular resolution, improving the quality of artificial vision.


Subject(s)
Electric Stimulation , Retina/physiology , Retinal Ganglion Cells , Visual Prosthesis , Animals , Blindness/rehabilitation , Electrodes, Implanted , Macaca mulatta , Neurodegenerative Diseases/pathology , Neurodegenerative Diseases/therapy , Photic Stimulation , Photoreceptor Cells/pathology , Prosthesis Design , Retina/cytology , Visual Fields
8.
J Neurophysiol ; 118(3): 1457-1471, 2017 09 01.
Article in English | MEDLINE | ID: mdl-28566464

ABSTRACT

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.


Subject(s)
Axons/physiology , Neural Prostheses , Retinal Ganglion Cells/physiology , Animals , Electric Stimulation , Evoked Potentials , Female , Macaca mulatta , Male , Sensory Thresholds
SELECTION OF CITATIONS
SEARCH DETAIL
...