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Sara Patterson, James A Kuchenbecker, James Anderson, Maureen Neitz, Jay Neitz; An S-cone amacrine cell in the primate retina sets the circadian clock at sunrise and sunset. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1373.
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© ARVO (1962-2015); The Authors (2016-present)
Circadian rhythm photoentrainment begins in the retina, with intrinsically photosensitive retinal ganglion cells (ipRGCs). Their intrinsic photopigment, melanopsin, mediates responses to long exposure, high irradiance light, while cone photoreceptor pathways provide the dominant input at lower light levels. In the primate retina, M1 ipRGCs have LM-ON/S-OFF cone opponency, yet the source of the S-OFF signal is unknown. We hypothesized that the S-OFF response is mediated by inhibitory input from an undiscovered S-cone amacrine cell (SCAC).
We tested this hypothesis by combining serial electron microscopy with single cell electrophysiology in the macaque monkey retina. The neurons and synapses of the S-cone connectome were reconstructed from a volume of central retina. A computational model was created from the response properties of cone inputs to ipRGCs measured with extracellular and whole cell recordings in a flatmount, ex vivo preparation.
By tracing neurons post-synaptic to S-ON bipolar cell (BC) ribbon synapses, we identified a population of displaced ACs receiving exclusively S-cone input. Five SCACs were reconstructed, each narrowly co-stratifying with, and selectively contacting, up to seven S-ON BCs. M1 ipRGCs were indeed a target of SCAC inhibitory synapses, and, in some cases, SCAC dendrites broke the retina's stratification rules, reaching into the ganglion cell layer to make additional synapses onto ipRGC somas. We confirmed the previously reported cone opponency in M1 ipRGC spike responses. Consistent with AC input, the S-cone response was present in voltage clamp recordings of the inhibitory, but not excitatory, synaptic input. Our model confirmed ipRGCs are strongly modulated by local LM:S-cone contrast in natural scenes at sunrise and sunset.
Here, we show that the primordial S-cone to S-ON BC pathway extends to the inner retina, with an amacrine cell receiving only S-ON BC input. Accordingly, we propose SCACs are part of an evolutionarily ancient color vision circuit, not for hue perception, but circadian photoentrainment. The spectral content of the environment changes during the day, with peaks in LM:S-cone contrast at sunrise and sunset. Furthermore, LM/S-cone opponency provides a reliable source of information for tracking twilight. Our results demonstrate cone inputs to ipRGCs are well-suited to encode the chromatic cues around dawn and dusk.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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