Nonselective Wiring Accounts for Red-Green Opponency in Midget Ganglion Cells of the Primate Retina

Abstract

In primate retina, "red-green" color coding is initiated when signals originating in long (L) and middle (M) wavelength-sensitive cone photoreceptors interact antagonistically. The center-surround receptive field of "midget" ganglion cells provides the neural substrate for L versus M cone-opponent interaction, but the underlying circuitry remains unsettled, centering around the longstanding question of whether specialized cone wiring is present. To address this question, we measured the strength, sign, and spatial tuning of L- and M-cone input to midget receptive fields in the peripheral retina of macaque primates of either sex. Consistent with previous work, cone opponency arose when one of the cone types showed a stronger connection to the receptive field center than to the surround. We implemented a difference-of-Gaussians spatial receptive field model, incorporating known biology of the midget circuit, to test whether physiological responses we observed in real cells could be captured entirely by anatomical nonselectivity. When this model sampled nonselectively from a realistic cone mosaic, it accurately reproduced key features of a cone-opponent receptive field structure, and predicted both the variability and strength of cone opponency across the retina. The model introduced here is consistent with abundant anatomical evidence for nonselective wiring, explains both local and global properties of the midget population, and supports a role in their multiplexing of spatial and color information. It provides a neural basis for human chromatic sensitivity across the visual field, as well as the maintenance of normal color vision despite significant variability in the relative number of L and M cones across individuals. Red-green color vision is a hallmark of the human and nonhuman primate that starts in the retina with the presence of long (L)- and middle (M)-wavelength sensitive cone photoreceptor types. Understanding the underlying retinal mechanism for color opponency has focused on the broad question of whether this characteristic can emerge from nonselective wiring, or whether complex cone-type-specific wiring must be invoked. We provide experimental and modeling support for the hypothesis that nonselective connectivity is sufficient to produce the range of red-green color opponency observed in midget ganglion cells across the retina. Our nonselective model reproduces the diversity of physiological responses of midget cells while also accounting for systematic changes in color sensitivity across the visual field.

Connectomic identification and three-dimensional color tuning of S-OFF midget ganglion cells in the primate retina

“…ON and OFF midget cells were considered opponent when L-and M-cone responses differed in sign (e.g., -R L ,+R M or +R L ,-R M ), and nonopponent when responses had the same sign (e.g., +R L ,+R M or -R L ,-R M ). Consistent with our previous recordings in near-peripheral retina (Wool, 2018), our midget cell population was heterogeneously composed of both L-M opponent (195 OFF, 44 ON) and nonopponent (61 OFF, 22 ON) cells (Fig. 7A).…”

“…Tuning curves were then fitted using a difference-of-Gaussians model (Enroth-Cugell et al, 1983) to determine the spatial arrangement of S and/or L+M inputs to the receptive field center and surround. Details and application of this model have been described previously (Dacey et al, 2000;McMahon et al, 2004;Wool et al, 2018). From the fitted tuning curves, the frequency of peak response, f peak , and the cutoff frequency, f cutoff (defined as the frequency at which response amplitude decreases to 1/√2 of the maximum) were computed for each cell for each stimulus.…”

“…The distinction between midget ganglion cells and blue ON cells is also clear due to the blue ON cell's distinctive response to S-cone stimuli and its large receptive field size (Crook et al, 2009), as considered further below. As inputs to midget ganglion cells increase as a function of eccentricity (Wool et al, 2018), cells in our recording locations sample anywhere from 3 to 12 cones, theoretically maximizing the likelihood of encountering an S cone in a cell's receptive field. Receptive-field mapping (see Methods) was used to differentiate midget ganglion cells from their larger (2-3×) blue ON counterparts.…”

“…OFF midget cells with proportional S-cone input of >0.10 comprised 45.9% (28/61) of all nonopponent OFF midget cells, but only 21.5% (42/195) of opponent OFF cells. Since the likelihood of encountering opponent or nonopponent midget cells is itself a function of eccentricity (Wool et al, 2018), we assessed whether this difference in detectable S-cone input between op- ponent and nonopponent OFF midget cells could also be attributed to a difference in retinal location. We found the mean eccentricity between these groups to be statistically indistinguishable (nonopponent cells: 33.3±6.6°, n = 24; opponent cells: 30.7±6.8°, n = 34; p = 0.15, Student's t test).…”

An S-cone circuit for edge detection in the primate retina

“…Midget RGCs make up over 90% of all RGCs in the central retina 77 and were confirmed by small soma, sustained responses and small centersurround receptive fields. 15,80 OFF RGC somas were generally vitread to ON RGC somas. In addition to these criteria, S-OFF midget RGCs were identified using small S-cone isolating stimuli positioned over the receptive field center.…”