Circadian Regulation of the Rod Contribution to Mesopic Vision in Mice

At intermediate (mesopic) light levels, rods and cones are both active and can contribute to vision. This presents a challenge to the retina because the visual responses originating with rods and cones are distinct, yet their visual responses must be seamlessly combined. The current study aimed to establish how the circadian clock regulates rod and/or cone vision in these conditions, given the strong time-of-day change in the reliance on each photoreceptor. Visual responses were recorded in the retina and visual thalamus of anaesthetized male mice at distinct circadian time points, and the method of receptor silent substitution was used to selectively stimulate different photoreceptor types. With stimuli designed to only activate rods, responses in the mesopic range were highly rhythmic and peaked in amplitude in the subjective night. This rhythm was abolished following intravitreal injection of the gap junction blocker meclofenamic acid, consistent with a circadian variation in the strength of electrical coupling of photoreceptors. In contrast, responses to stimuli designed to only activate cones were arrhythmic within the mesopic to photopic range when adapted to the background irradiance. The outcome was that combined rod-plus-cone responses showed a stable contrast-response relationship across mesopic-photopic backgrounds in the circadian day, whereas at night, responses were significantly amplified at lower light levels. These data support the idea that the circadian clock is a key regulator of vision, in this case defining the relative amplitude of rod/cone vision across the mesopic transition according to time of day.SIGNIFICANCE STATEMENT Although the importance of circadian clocks in regulating vision has been long recognized, less is known about how the clock shapes vision in conditions where both rods and cones are active (mesopic conditions). Here, the novel approach of receptor silent substitution has been applied to trace rod and cone visual responses in mice across the circadian cycle and has identified pronounced rhythms in rod, but not cone, vision. This has the effect of boosting responses in dimmer backgrounds at night at the cost of impaired contrast-response stability across the mesopic to photopic range. Thus, the circadian clock drives anticipatory changes in the relative contribution of rods versus cones to vision, which match the prevailing visual environment.