Table 1.
Human retinas used for this study.
Fig 1.
Population response of human retinal ganglion cells.
(A) Drifting gratings with 4 temporal frequencies and 6 spatial frequencies. (B) Response strength (amplitude of the Fourier transform (FT) at the stimulus frequency, normalized to maximal response) to 24 drifting sinusoidal gratings with different spatial and temporal frequencies, averaged across N = 293 cells (top). Distribution of preferred spatial (left) and temporal (right) frequencies in response to drifting gratings, N = 288 cells (bottom). (C) Full-field “chirp” frequency ramp from 0.5 to 8 Hz and full-field “chirp” contrast ramp. (D) Normalized response strength (FTresponse/FTstimulus) to a full-field frequency ramp (“chirp”), in different frequency bands (Box-whisker-plots: mean, quartiles, maximum and minimum; N = 141 cells). (E) Bar moving with 6 different speeds. (F) Distribution of the median preferred speed measured with a single moving bar, N = 37 cells. (G) Full-field flash contrast steps consisting of two positive and two negative contrast steps. (H) Proportion of ganglion cells responding to positive full-field contrast steps (ON), negative contrast steps (OFF) or both (ON-OFF), N = 121 cells.
Fig 2.
Example response properties of human ganglion cells.
A) ON-cells, B) OFF-cells, C) ON-OFF-cells. Column 1: average firing rates (top) and raster plots (bottom) to full-field contrast steps; column 2: response to bar moving with different speeds; column 3: activity during a full-field chirp contrast ramp at 2 Hz; column 4: response to “chirp stimulus” (full-field temporal frequency modulation from 0.5 to 8 Hz); column 5: normalized response strengths to 24 sinusoidal drifting-gratings (convention as in Fig 1B); column 6: firing rate for the sinusoidal drifting-grating causing maximal response (black square in column 5). Stimuli are depicted on top. Colors correspond to Fig 5. Empty space indicates that the stimulus was not presented to this cell. Firing rates plotted in gray indicate that this cell did not respond consistently to this stimulus.
Fig 3.
Human retinal ganglion cells show similar spatial and temporal frequency response curves as non-human primate retinal ganglion cells.
(A) Heat map: Average responsivity of human retinal ganglion cells for drifting sinusoidal gratings, replicated from Fig 1E (N = 293). Curves: Spatial frequency (top) and temporal frequency (left) response curves (mean across all cells). (B, C) Spatial and temporal response curve in comparison with published data on non-human primate ganglion cells. Non-human primate data adapted from [40] (midget); [41, 42] (parasol); [41, 43] (blue-yellow); [25] (upsilon); [28] (melanopsin).
Fig 4.
Schematic of clustering process.
Cell responses were clustered in a 5-step process. Clustering was focused on cells that were probed with the chirp stimulus. All cells with response to the chirp were assigned to the 5 Cowan clusters if their responses matched (step 1 and 2, cluster 1–5), otherwise they were grouped based on their flash responses (step 3, clusters 6–8). Cells without chirp responses were clustered based on their drifting-grating responses (step 4, clusters 9–16). Cells that were not probed with the chirp stimulus were assigned to one of the 16 clusters based on their drifting-grating responses (step 5). At each step, a few cells dropped out if they did not fit the parameters of the current nor the next step. E.g. cells that did not experience the chirp stimulus and did not respond to the drifting-grating stimulus did not enter the 5 step process (17 cells).
Fig 5.
Clusters of human retinal ganglion cells.
(A) Clusters of cells that putatively correspond to the five dominant primate retinal ganglion cell types, assigned based on their chirp and flash responses. (B) Clusters with chirp responses that do not fit cluster 1–5. Cells were clustered based on their flash responses. (C) Clusters of cells without chirp responses were clustered based on their drifting-grating responses. The remaining cells that were not probed with the chirp stimulus were assigned to the previous 16 clusters based on their drifting-grating responses. (A1, B1, C1) Left: Name of each cluster, number n and percentage of cells relative to total of light-sensitive cells that were probed with the chirp stimulus. n_all includes cells that were not probed with the chirp stimulus but assigned based on their drifting-grating responses. Right: Heatmap of responses to the flash stimulus of all cells in each cluster (spontaneous background firing rate subtracted; horizontal axis is time; each line is one cell). Colored bars here and in A2 indicate the cells with a flash response, the color corresponds to the scheme used in Cowan et al. 2020 [45]. Above the heatmap, the cluster average is shown in black for cells with flash responses and in gray for the remaining cells. (A2, B2, C2) Normalized responses of all cells in each cluster to the chirp stimulus (heatmap, 1 line per cell, black indicates max. response). Numbers on the right refer to the example cells in Fig 2. (A3, B3, C3) Average, normalized response to the set of 24 drifting-grating stimuli for all cells in each cluster. (A4, B4, C4) Distribution of four indices for each cell (gray) in the cluster. Example cells form Fig 2 are indicated in color. Solid lines indicate median values. Chirp frequency index: <0 indicates preference for lower temporal frequencies in the chirp stimulus, >0 indicates a preference for higher temporal frequencies. Contrast preference index: <0 indicates a preference for the lower contrast part of the chirp stimulus, >0 a preference for higher contrasts. Spatial preference and temporal preference: the values indicate the location of the peak of a Gaussian fit to the drifting-grating heatmap.
Table 2.
Response behavior of clustered human retinal ganglion cells.
Fig 6.
Donated human retinas are healthy.
(A) Multi-electrode array layout (gray) and electrodes with sortable, light-responsive cells (green) of two example experiments. Responding cells are distributed across the recorded retinal pieces. (B) Distribution of peak firing rates in response to full-field contrast steps. (C1) Top: Number of cells responding at any given time point (gray bars) was similar to the total number that had responses until that time point (horizontal lines). Bottom: Mean ± standard deviation of peak firing rate for the responding cells. Data from a subset of experiments that lasted for 2.5h (N = 4 experiments, N = 52 cells). (C2) Example firing rate traces for one cell. (D) Spontaneous background firing rates (mean ± standard deviation) of the same cells and time points as in C1. (E) Number of responding units and ischemia time for donors without (black) and with (gray) known adverse condition (indicated in Table 1). (F) Number of responding cells for individual stimuli as a function of ischemia time. Lines indicate linear fits. (G) Total number of responding cells and responses per stimulus for donors with and without known adverse condition. Lines indicate median numbers.