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S. Weng, K. Y. Wong, D. M. Berson; Circadian Modulation of Ganglion-Cell Phototransduction. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5785. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Intrinsically photosensitive retinal ganglion cells (ipRGCs) synchronize the central circadian pacemaker to the solar cycle. It is unknown whether the photosensitivity of these cells is subject to circadian modulation, as image-forming retinal networks are. Because such modulation could affect the phase-dependence of photic clock resetting, we sought to learn whether intrinsic, melanopsin-driven photoresponses show circadian oscillations.
Adult rats were entrained to a 12 hr: 12 hr light-dark (LD) cycle, then kept in constant darkness (DD) for 12-60 hr preceding retinal harvest to minimize effects of light adaptation. Circadian time (CT) at harvest was extrapolated from the last LD cycle assuming period (tau) to be 24.1 hr. Retinas were isolated in dim red light and mounted on multielectrode arrays. Rod/cone signals were silenced with glutamate receptor blockers so that light activated only ipRGCs, recognizable from their sluggish, sustained, and slowly terminating photoresponses. Sensitivity was probed with an ascending series of 10 s white-light stimuli.
Intensity-response functions were indistinguishable among 3 of the 4 phases tested: early day (CT0-1), midday (CT6-7), and midnight (CT18-19). In the early night (CT12-13), however, responses to the brightest stimuli were significantly, if modestly, elevated (~20%). This reflected an increase in response gain rather than in sensitivity because threshold was unchanged.
Circadian modulation of ipRGCs’ intrinsic photoresponses is modest, consisting of slightly augmented response gain early in subjective night. This may be related to the rise in melanopsin mRNA and protein levels at roughly this circadian phase (e.g., Sakamoto et al., 2005). However, the decrease in threshold that this would predict is not observed and other mechanisms may dominate. Our results suggest that intraretinal rhythms in ipRGC photosensitivity contribute little to the mechanism by which circadian phase gates the photic resetting of the central clock. Modulation of extrinsic, synaptic inputs to ipRGCs remain a possibility.
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