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. 2013 Apr 24;33(17):7194-205.
doi: 10.1523/JNEUROSCI.4967-12.2013.

Focal electrical stimulation of major ganglion cell types in the primate retina for the design of visual prostheses

Lauren H Jepson  1 , Pawel Hottowy, Keith Mathieson, Deborah E Gunning, Wladyslaw Dabrowski, Alan M Litke, E J Chichilnisky
Affiliations

Focal electrical stimulation of major ganglion cell types in the primate retina for the design of visual prostheses

Lauren H Jepson et al. J Neurosci. .

Abstract

Electrical stimulation of retinal neurons with an advanced retinal prosthesis may eventually provide high-resolution artificial vision to the blind. However, the success of future prostheses depends on the ability to activate the major parallel visual pathways of the human visual system. Electrical stimulation of the five numerically dominant retinal ganglion cell types was investigated by simultaneous stimulation and recording in isolated peripheral primate (Macaca sp.) retina using multi-electrode arrays. ON and OFF midget, ON and OFF parasol, and small bistratified ganglion cells could all be activated directly to fire a single spike with submillisecond latency using brief pulses of current within established safety limits. Thresholds for electrical stimulation were similar in all five cell types. In many cases, a single cell could be specifically activated without activating neighboring cells of the same type or other types. These findings support the feasibility of direct electrical stimulation of the major visual pathways at or near their native spatial and temporal resolution.

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Figures

Figure 1.
Figure 1.
Identification of major RGC types in primate retina using visual response properties. Center, Receptive field (RF) diameter and the first principal component (PC1) of the STA time course were used to subdivide the cells recorded in a single preparation into distinct groups. Surrounding, RFs of cells in each group tiled visual space. Ellipses depict the 1.25 SD boundaries of Gaussian fits to the spatial component of the STA (see Materials and Methods). Hexagons represent the outline of the electrode array and filled gray circles indicate electrode positions. Some cells with RFs lying outside the array boundary were detected based on axonal signals (see Materials and Methods).
Figure 2.
Figure 2.
Cells from each of the five major primate RGC types exhibited single-spike, submillisecond responses to electrical stimulation and could be activated without activating neighboring cells of the same type. A, Overlaid raw (inset) and artifact-subtracted voltage traces (main axes) recorded during and immediately after 50 stimulation trials, with successes (traces containing a spike) in red and failures (traces containing only stimulus artifact) in solid black. Black dashed traces show the spike template of each cell, taken from the electrical image (see Materials and Methods). Voltage traces were recorded by the electrode used for stimulation in all examples except the OFF parasol, in which voltage traces were recorded by a neighboring electrode. Scale bars: Insets, 0.5 ms and 100 μV. B, Raster plots of responses shown in A, with spike time defined as the negative peak of the spike waveform. C, Response probabilities measured over a range of pulse amplitudes, fit by a sigmoidal function (see Materials and Methods). For each cell, open circle indicates pulse amplitude applied in A and B, and “x ” indicates amplitude applied in D. D, Selective activation of the example cell among neighboring cells of the same type. Each cell is represented by an elliptical fit to its receptive field, and the color of the fit indicates the fraction of trials in which the current pulse elicited a response.
Figure 3.
Figure 3.
All cells activated by electrical stimulation responded with a precisely timed spike within 1 ms of stimulus onset. The PSTH of a representative cell from each cell type is shown with corresponding curve fit in black (see Materials and Methods). Fits to the PSTHs of all other cells are shown in gray. Spike times are defined by the negative peak of the spike waveform.
Figure 4.
Figure 4.
ON and OFF parasol and midget cells in a single preparation exhibited similar activation thresholds. Response curve of one representative cell of each type is shown. Receptive fields of cells positioned over the array are depicted as elliptical fits (Fig. 1). Receptive fields of different cell types are plotted separately for clarity, with the array boundary indicated by the hexagonal outlines. The receptive field of the cell for which the response curve is given is indicated with a solid fill. The position of each corresponding stimulation electrode is depicted as an open black circle and the positions of the remaining electrodes are indicated with filled gray circles.
Figure 5.
Figure 5.
Comparison of measured activation thresholds of different cell types within four preparations. A, Thresholds of all activated cells from the preparation represented in Figure 4. Thresholds corresponding to example response curves shown in Figure 4 are marked with triangles. B–D, Measured thresholds for all cells from examined cell types in three additional retinal preparations. Values in parentheses indicate the fraction of cells lying over the array with measurable thresholds. Dashed vertical lines mark the conservative platinum charge density limit of 0.1 mC/cm2 (see Discussion) based on the mean planar area of the electrodes used in each preparation. Gray regions indicate untested ranges of pulse amplitudes.
Figure 6.
Figure 6.
Examples of cell selectivity in electrical activation. A, C, and E, Response probability of each cell in a single recording for a specific stimulation electrode and pulse amplitude. Cells are represented by elliptical fits to their visual receptive fields (Fig. 1), and each target cell is marked with an arrow. Fill colors indicate response probabilities. Mosaics of receptive fields are separated and midget mosaics are enlarged 25% relative to parasol mosaics for clarity. The position of each stimulation electrode is depicted as an open black circle, and non-stimulation electrodes are shown as filled gray circles. The outline of the array is indicated with a hexagon. B, D, and F, Response curves of activated cells. Vertical dashed lines indicate pulse amplitudes plotted in A, C, and E. Nonzero response probabilities for cells in A, C, and E not represented in B, D, and F were ≤0.08 and were consistent with spontaneous activity (see Materials and Methods).
Figure 7.
Figure 7.
Approximately half of the midget cells in two preparations could be activated without also activating any other midget or parasol cells in the region. Each gray region indicates the analyzed range of pulse amplitudes for the stimulation electrode chosen to activate a particular target cell. Circles and horizontal bars show the threshold and activation range of each activated cell, with target cells in black and non-target cells in red. The activation range was defined as the range of charge amplitudes that resulted in response probabilities between 0.2 and 0.8 (lower right inset). Selectivity attempts marked with i, ii, and iii correspond to examples in Figure 6A/B, C/D, and E/F, respectively.
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