Joanna D. Crook

Y-cell receptive field and collicular projection of parasol ganglion cells in macaque monkey retina.

The distinctive parasol ganglion cell of the primate retina transmits a transient, spectrally nonopponent signal to the magnocellular layers of the lateral geniculate nucleus. Parasol cells show well-recognized parallels with the α-Y cell of other mammals, yet two key α-Y cell properties, a collateral projection to the superior colliculus and nonlinear spatial summation, have not been clearly established for parasol cells. Here, we show by retrograde photodynamic staining that parasol cells project to the superior colliculus. Photostained dendritic trees formed characteristic spatial mosaics and afforded unequivocal identification of the parasol cells among diverse collicular-projecting cell types. Loose-patch recordings were used to demonstrate for all parasol cells a distinct Y-cell receptive field “signature” marked by a nonlinear mechanism that responded to contrast-reversing gratings at twice the stimulus temporal frequency [second Fourier harmonic (F2)] independent of stimulus spatial phase. The F2 component showed high contrast gain and temporal sensitivity and appeared to originate from a region coextensive with that of the linear receptive field center. The F2 spatial frequency response peaked well beyond the resolution limit of the linear receptive field center, showing a Gaussian center radius of ∼15 μm. Blocking inner retinal inhibition elevated the F2 response, suggesting that amacrine circuitry does not generate this nonlinearity. Our data are consistent with a pooled-subunit model of the parasol Y-cell receptive field in which summation from an array of transient, partially rectifying cone bipolar cells accounts for both linear and nonlinear components of the receptive field.

Parallel ON and OFF cone bipolar inputs establish spatially coextensive receptive field structure of blue-yellow ganglion cells in primate retina.

In the primate retina the small bistratified, “blue-yellow” color-opponent ganglion cell receives parallel ON-depolarizing and OFF-hyperpolarizing inputs from short (S)-wavelength sensitive and combined long (L)- and middle (M)-wavelength sensitive cone photoreceptors, respectively. However, the synaptic pathways that create S versus LM cone-opponent receptive field structure remain controversial. Here, we show in the macaque monkey retina in vitro that at photopic light levels, when an identified rod input is excluded, the small bistratified cell displays a spatially coextensive receptive field in which the S-ON-input is in spatial, temporal, and chromatic balance with the LM-OFF-input. ON pathway block with l-AP-4, the mGluR6 receptor agonist, abolished the S-ON response but spared the LM-OFF response. The isolated LM component showed a center-surround receptive field structure consistent with an input from OFF-center, ON-surround “diffuse” cone bipolar cells. Increasing retinal buffering capacity with HEPES attenuated the LM-ON surround component, consistent with a non-GABAergic outer retina feedback mechanism for the bipolar surround. The GABAa/c receptor antagonist picrotoxin and the glycine receptor antagonist strychnine did not affect chromatic balance or the basic coextensive receptive field structure, suggesting that the LM-OFF field is not generated by an inner retinal inhibitory pathway. We conclude that the opponent S-ON and LM-OFF responses originate from the excitatory receptive field centers of S-ON and LM-OFF cone bipolar cells, and that the LM-OFF- and ON-surrounds of these parallel bipolar inputs largely cancel, explaining the small, spatially coextensive but spectrally antagonistic receptive field structure of the blue-ON ganglion cell.

Horizontal Cell Feedback without Cone Type-Selective Inhibition Mediates “Red–Green” Color Opponency in Midget Ganglion Cells of the Primate Retina

The distinctive red–green dimension of human and nonhuman primate color perception arose relatively recently in the primate lineage with the appearance of separate long (L) and middle (M) wavelength-sensitive cone photoreceptor types. “Midget” ganglion cells of the retina use center–surround receptive field structure to combine L and M cone signals antagonistically and thereby establish a “red–green, color-opponent” visual pathway. However, the synaptic origin of red–green opponency is unknown, and conflicting evidence for either random or L versus M cone-selective inhibitory circuits has divergent implications for the developmental and evolutionary origins of trichromatic color vision. Here we directly measure the synaptic conductances evoked by selective L or M cone stimulation in the midget ganglion cell dendritic tree and show that L versus M cone opponency arises presynaptic to the midget cell and is transmitted entirely by modulation of an excitatory conductance. L and M cone synaptic inhibition is feedforward and thus occurs in phase with excitation for both cone types. Block of GABAergic and glycinergic receptors does not attenuate or modify L versus M cone antagonism, discounting both presynaptic and postsynaptic inhibition as sources of cone opponency. In sharp contrast, enrichment of retinal pH-buffering capacity, to attenuate negative feedback from horizontal cells that sum L and M cone inputs linearly and without selectivity, completely abolished both the midget cell surround and all chromatic opponency. Thus, red–green opponency appears to arise via outer retinal horizontal cell feedback that is not cone type selective without recourse to any inner retinal L versus M cone inhibitory pathways.

The Smooth Monostratified Ganglion Cell: Evidence for Spatial Diversity in the Y-Cell Pathway to the Lateral Geniculate Nucleus and Superior Colliculus in the Macaque Monkey

In the primate visual system approximately 20 morphologically distinct pathways originate from retinal ganglion cells and project in parallel to the lateral geniculate nucleus (LGN) and/or the superior colliculus. Understanding of the properties of these pathways and the significance of such extreme early pathway diversity for later visual processing is limited. In a companion study we found that the magnocellular LGN-projecting parasol ganglion cells also projected to the superior colliculus and showed Y-cell receptive field structure supporting the hypothesis that the parasol cells are analogous to the well studied alpha-Y cell of the cats retina. We here identify a novel ganglion cell class, the smooth monostratified cells, that share many properties with the parasol cells. Smooth cells were retrogradely stained from tracer injections made into either the LGN or superior colliculus and formed inner-ON and outer-OFF populations with narrowly monostratified dendritic trees that surprisingly appeared to perfectly costratify with the dendrites of parasol cells. Also like parasol cells, smooth cells summed input from L- and M-cones, lacked measurable S-cone input, showed high spike discharge rates, high contrast and temporal sensitivity, and a Y-cell type nonlinear spatial summation. Smooth cells were distinguished from parasol cells however by smaller cell body and axon diameters but ∼2 times larger dendritic tree and receptive field diameters that formed a regular but lower density mosaic organization. We suggest that the smooth and parasol populations may sample a common presynaptic circuitry but give rise to distinct, parallel achromatic spatial channels in the primate retinogeniculate pathway.

Nonselective wiring accounts for red-green opponency in midget ganglion cells of the primate retina

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. SIGNIFICANCE STATEMENT 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.

The smooth monostratified ganglion cell

In the primate visual system approximately 20 morphologically distinct pathways originate from retinal ganglion cells and project in parallel to the lateral geniculate nucleus (LGN) and/or the superior colliculus. Understanding of the properties of these pathways and the significance of such extreme early pathway diversity for later visual processing is limited. In a companion study we found that the magnocellular LGN-projecting parasol ganglion cells also projected to the superior colliculus and showed Y-cell receptive field structure supporting the hypothesis that the parasol cells are analogous to the well studied alpha-Y cell of the cats retina. We here identify a novel ganglion cell class, the smooth monostratified cells, that share many properties with the parasol cells. Smooth cells were retrogradely stained from tracer injections made into either the LGN or superior colliculus and formed inner-ON and outer-OFF populations with narrowly monostratified dendritic trees that surprisingly appeared to perfectly costratify with the dendrites of parasol cells. Also like parasol cells, smooth cells summed input from L- and M-cones, lacked measurable S-cone input, showed high spike discharge rates, high contrast and temporal sensitivity, and a Y-cell type nonlinear spatial summation. Smooth cells were distinguished from parasol cells however by smaller cell body and axon diameters but ∼2 times larger dendritic tree and receptive field diameters that formed a regular but lower density mosaic organization. We suggest that the smooth and parasol populations may sample a common presynaptic circuitry but give rise to distinct, parallel achromatic spatial channels in the primate retinogeniculate pathway.

The smooth monostratified ganglion cell: evidence for spatial diversity in the Y-cell pathway to the LGN and superior colliculus in the macaque monkey

In the primate visual system approximately 20 morphologically distinct pathways originate from retinal ganglion cells and project in parallel to the lateral geniculate nucleus (LGN) and/or the superior colliculus. Understanding of the properties of these pathways and the significance of such extreme early pathway diversity for later visual processing is limited. In a companion study we found that the magnocellular LGN-projecting parasol ganglion cells also projected to the superior colliculus and showed Y-cell receptive field structure supporting the hypothesis that the parasol cells are analogous to the well studied alpha-Y cell of the cats retina. We here identify a novel ganglion cell class, the smooth monostratified cells, that share many properties with the parasol cells. Smooth cells were retrogradely stained from tracer injections made into either the LGN or superior colliculus and formed inner-ON and outer-OFF populations with narrowly monostratified dendritic trees that surprisingly appeared to perfectly costratify with the dendrites of parasol cells. Also like parasol cells, smooth cells summed input from L- and M-cones, lacked measurable S-cone input, showed high spike discharge rates, high contrast and temporal sensitivity, and a Y-cell type nonlinear spatial summation. Smooth cells were distinguished from parasol cells however by smaller cell body and axon diameters but ∼2 times larger dendritic tree and receptive field diameters that formed a regular but lower density mosaic organization. We suggest that the smooth and parasol populations may sample a common presynaptic circuitry but give rise to distinct, parallel achromatic spatial channels in the primate retinogeniculate pathway.