Search

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., (Copyright © 2017 the American Physiological Society.)

Amacrine cells are the most diverse and least understood cell class in the retina. Polyaxonal amacrine cells (PACs) are a unique subset identified by multiple long axonal processes. To explore their functional properties, populations of PACs were identified by their distinctive radially propagating spikes in large-scale high-density multielectrode recordings of isolated macaque retina. One group of PACs exhibited stereotyped functional properties and receptive field mosaic organization similar to that of parasol ganglion cells. These PACs had receptive fields coincident with their dendritic fields, but much larger axonal fields, and slow radial spike propagation. They also exhibited ON-OFF light responses, transient response kinetics, sparse and coordinated firing during image transitions, receptive fields with antagonistic surrounds and fine spatial structure, nonlinear spatial summation, and strong homotypic neighbor electrical coupling. These findings reveal the functional organization and collective visual signaling by a distinctive, high-density amacrine cell population.

Topographic maps are the primary means of relaying spatial information in the brain. Understanding the mechanisms by which they form has been a goal of experimental and theoretical neuroscientists for decades. The projection of the retina to the superior colliculus (SC)/tectum has been an important model used to show that graded molecular cues and patterned retinal activity are required for topographic map formation. Additionally, interaxon competition has been suggested to play a role in topographic map formation; however, this view has been recently challenged. Here we present experimental and computational evidence demonstrating that interaxon competition for target space is necessary to establish topography. To test this hypothesis experimentally, we determined the nature of the retinocollicular projection in Math5 (Atoh7) mutant mice, which have severely reduced numbers of retinal ganglion cell inputs into the SC. We find that in these mice, retinal axons project to the anteromedialj portion of the SC where repulsion from ephrin-A ligands is minimized and where their attraction to the midline is maximized. This observation is consistent with the chemoaffinity model that relies on axon-axon competition as a mapping mechanism. We conclude that chemical labels plus neural activity cannot alone specify the retinocollicular projection; instead axon-axon competition is necessary to create a map. Finally, we present a mathematical model for topographic mapping that incorporates molecular labels, neural activity, and axon competition.

Objective: Retinal prostheses must be able to activate cells in a selective way in order to restore high-fidelity vision. However, inadvertent activation of far-away retinal ganglion cells (RGCs) through electrical stimulation of axon bundles can produce irregular and poorly controlled percepts, limiting artificial vision. In this work, we aim to provide an algorithmic solution to the problem of detecting axon bundle activation with a bi-directional epiretinal prostheses. Methods: The algorithm utilizes electrical recordings to determine the stimulation current amplitudes above which axon bundle activation occurs. Bundle activation is defined as the axonal stimulation of RGCs with unknown soma and receptive field locations, typically beyond the electrode array. The method exploits spatiotemporal characteristics of electrically-evoked spikes to overcome the challenge of detecting small axonal spikes. Results: The algorithm was validated using large-scale, single-electrode and short pulse, ex vivo stimulation and recording experiments in macaque retina, by comparing algorithmically and manually identified bundle activation thresholds. For 88% of the electrodes analyzed, the threshold identified by the algorithm was within ±10% of the manually identified threshold, with a correlation coefficient of 0.95. Conclusion: This works presents a simple, accurate and efficient algorithm to detect axon bundle activation in epiretinal prostheses. Significance: The algorithm could be used in a closed-loop manner by a future epiretinal prosthesis to reduce poorly controlled visual percepts associated with bundle activation. Activation of distant cells via axonal stimulation will likely occur in other types of retinal implants and cortical implants, and the method may therefore be broadly applicable. [ABSTRACT FROM AUTHOR]

This study combines for the first time two major approaches to understanding the function and structure of neural circuits: large-scale multielectrode recordings, and confocal imaging of labeled neurons. To achieve this end, we develop a novel approach to the central problem of anatomically identifying recorded cells, based on the electrical image: the spatiotemporal pattern of voltage deflections induced by spikes on a large-scale, high-density multielectrode array. Recordings were performed from identified ganglion cell types in the macaque retina. Anatomical images of cells in the same preparation were obtained using virally transfected fluorescent labeling or by immunolabeling after fixation. The electrical image was then used to locate recorded cell somas, axon initial segments, and axon trajectories, and these signatures were used to identify recorded cells. Comparison of anatomical and physiological measurements permitted visualization and physiological characterization of numerically dominant ganglion cell types with high efficiency in a single preparation. [ABSTRACT FROM AUTHOR]

Summary: During development, retinal axons project coarsely within their visual targets before refining to form organized synaptic connections. Spontaneous retinal activity, in the form of acetylcholine-driven retinal waves, is proposed to be necessary for establishing these projection patterns. In particular, both axonal terminations of retinal ganglion cells (RGCs) and the size of receptive fields of target neurons are larger in mice that lack the β2 subunit of the nicotinic acetylcholine receptor (β2KO). Here, using a large-scale, high-density multielectrode array to record activity from hundreds of RGCs simultaneously, we present analysis of early postnatal retinal activity from both wild-type (WT) and β2KO retinas. We find that β2KO retinas have correlated patterns of activity, but many aspects of these patterns differ from those of WT retina. Quantitative analysis suggests that wave directionality, coupled with short-range correlated bursting patterns of RGCs, work together to refine retinofugal projections. [Copyright &y& Elsevier]

The dynamic range of visual coding is extended by having separate ganglion cell types that respond to light increments and decrements. Although the primordial color vision system in mammals contains a well-characterized ganglion cell that responds to blue light increments (a blue On center cell), less is known about ganglion cells that respond to blue light decrements (blue Off center cells). We identified a regular mosaic of blue Off center ganglion cells in the ground squirrel. Contrary to the standard scheme, blue Off responses came from a blue On bipolar and inverting amacrine cell. [ABSTRACT FROM AUTHOR]