A remarkable feature of human vision is that the retina and brain have evolved circuitry to extract useful spatial and spectral information from signals originating in a photoreceptor mosaic with trichromatic constituents that vary widely in their relative numbers and local spatial configurations. A critical early transformation applied to cone signals is horizontal-cell-mediated lateral inhibition, which imparts a spatially antagonistic surround to individual cone receptive fields, a signature inherited by downstream neurons and implicated in color signaling. In the peripheral retina, the functional connectivity of cone inputs to the circuitry that mediates lateral inhibition is not cone-type specific, but whether these wiring schemes are maintained closer to the fovea remains unsettled, in part because central retinal anatomy is not easily amenable to direct physiological assessment. Here, we demonstrate how the precise topography of the long (L)-, middle (M)-, and short (S)-wavelength-sensitive cones in the human parafovea (1.5° eccentricity) shapes perceptual sensitivity. We used adaptive optics microstimulation to measure psychophysical detection thresholds from individual cones with spectral types that had been classified independently by absorptance imaging. Measured against chromatic adapting backgrounds, the sensitivities of L and M cones were, on average, receptor-type specific, but individual cone thresholds varied systematically with the number of preferentially activated cones in the immediate neighborhood. The spatial and spectral patterns of these interactions suggest that interneurons mediating lateral inhibition in the central retina, likely horizontal cells, establish functional connections with L and M cones indiscriminately, implying that the cone-selective circuitry supporting red-green color vision emerges after the first retinal synapse. [ABSTRACT FROM AUTHOR]