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

Abstract

The first step of color processing in the visual pathway of primates occurs when signals from short-(S), middle-(M) and long-(L) wavelength sensitive cone types interact antagonistically within the retinal circuitry to create color-opponent pathways. The midget (L vs. M or 'red-green') and small bistratified (S vs. L+M, or 'blue-yellow') appear to provide the physiological origin of the cardinal axes of human color vision. Here we confirm the presence of an additional S-OFF midget circuit in the macaque monkey fovea with scanning block-face electron microscopy (SBEM) and show physiologically that a subpopulation of S-OFF midget cells combine S, L and M cone inputs along non-cardinal directions of color space, expanding the retinal role in color coding. AbstractIn the trichromatic primate retina, the 'midget' retinal ganglion cell is the classical substrate for red-green color signaling, with a circuitry that enables antagonistic responses between long (L)-and medium (M)-wavelength sensitive cone inputs. Previous physiological studies show that some OFF midget ganglion cells may receive sparse input from short (S)-wavelength sensitive cones, but the effect of S-cone inputs on the chromatic tuning properties of such cells has been unexplored. Moreover, anatomical evidence for a synaptic pathway from S cones to OFF midget ganglion cells through OFF-midget bipolar cells remains ambiguous. In this study we address both questions for the macaque monkey retina. First, we used serial block-face electron microscopy (SBEM) to show that every S-cone in the parafoveal retina synapses principally with a single OFF-midget bipolar cell which in turn forms a private-line connection with an OFF midget ganglion cell. Second, we used patch electrophysiology to characterize the chromatic tuning of OFF midget ganglion cells in the near peripheral retina that receive combined input from L, M and S cones. These 'S-OFF' midget cells have a characteristic S-cone spatial signature, but demonstrate heterogeneous color properties due to variable strength of L, M, and S cone input across the receptive field. Together these findings strongly support the hypothesis that the OFF midget pathway is the major conduit for S-OFF signals in primate retina, and redefines the pathway as a chromatically complex substrate that encodes color signals beyond the classically recognized L vs. M and S vs. L+M cardinal mechanisms.

Diverse Cell Types, Circuits, and Mechanisms for Color Vision in the Vertebrate Retina

“…Beyond central retina, the impact of mixing S, L, and M cone inputs on the spectral tuning of S OFF midget cells is less clear, but it would predict that these cells might show sensitivity that does not lie strictly along the S versus LϩM cardinal axis (FIGURE 10D). In a recent study designed to test this idea directly, OFF midget ganglion cells were recorded in the near retinal periphery, and chromatic stimuli were modulated around a color circle in LϩM versus S cone opponent space (506). The results showed that all ON midget cells and the majority of OFF midgets lacked a measurable S cone input.…”

“…Over 50 years ago, action potential recordings from neurons in the parvocellular layers of the LGN by Hubel and Wiesel presented a tantalizingly simple picture of how a single visual pathway might be the neural basis for "opponent color theory" (498), the dominant idea in color science at that time. Today we are confronted with a dizzyingly complex array of pathways and mechanisms that play varied roles in color processing at the retinal level; indeed, new circuitries that may be fundamental to understanding human color vision are still being discovered (506). The motivation for this review is to consider our current understanding of the cell types and circuits of the retina across vertebrate species, from teleost fish like the zebrafish and goldfish, to intensively studied mammals like mouse and rabbit, and to human and non-human primates where certain aspects of color circuitry appear to have been reinvented during primate evolution.…”