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S. Weng, D. M. Berson; Sustained M-Cone and S-Cone Inputs to Ganglion-Cell Photoreceptors: Absence of Chromatic Opponency. Invest. Ophthalmol. Vis. Sci. 2010;51(13):666.
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© ARVO (1962-2015); The Authors (2016-present)
Intrinsically photosensitive retinal ganglion cells (ipRGCs) exhibit synaptically mediated ON responses driven by rods and cones. We wondered whether the cone influence on mouse ipRGCs derives from S or M cones and whether this circuit exhibits the M (&L)-ON, S-OFF chromatic opponency reported in primates (Dacey et al., 2005).
All experiments were done in connexin-36 knockout mice to isolate the cone-driven ON input by disrupting rod-mediated ON pathways. Retinas were isolated in dim red light, mounted on a 60-channel electrode array, and dark adapted (1 h). Cone inputs were evoked by full-field spectrally narrowband light steps of various intensities. At the end of the experiment, rod/cone networks were silenced with glutamate receptor blockers and ipRGCs identified by their persistent photoresponses. Spike trains from single cells were extracted by cluster analysis using Offline Sorter software.
Cone synaptic input was distinguishable from intrinsic, melanopsin-based photoresponses by its lower threshold (~1.5-2.0 log units), much faster onset and elimination by glutamatergic blockade. This cone response was surprisingly persistent, elevating the firing rate in steady illumination for at least 10 seconds. Short- and long-wavelength stimuli of matched photon flux density (400 nm vs. 500 nm) evoked comparable ON response in all ipRGCs, suggesting that S-cone and M-cone inputs to ipRGCs are of about equal strength and lack the chromatic opponency observed in primates.
Like most rodent ganglion cells, ipRGCs receive convergent excitatory input from both S and M cones. In contrast to the (M+L)-ON, S-OFF opponency in primate ipRGCs, cone influences are broadband (M-ON, S-ON) in mice and result in a broadband action spectrum in these cells under photopic conditions. The cone drive to ipRGCs is surprisingly sustained, matching the tonic nature of their rod input as well as their intrinsic, melanopsin-based phototransduction. This presumably reflects the unique temporal requirements of circadian photoentrainment and other non-image-forming photic responses.
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