Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester M13 9PT, United Kingdom
J Neurosci. 2022 Nov 23;42(47):8795-8806. doi: 10.1523/JNEUROSCI.0486-22.2022. Epub 2022 Oct 10.
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. 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.
在中间（中间）光水平，棒状和锥状均活跃，可有助于视力。这对视网膜提出了挑战，因为源自棒状和锥状的视觉反应是不同的，但是它们的视觉反应必须无缝地结合在一起。当前的研究旨在确定生物钟如何在这些条件下调节棒状和/或锥状视觉，因为每种光感受器的依赖性在一天中的时间变化很大。在不同的生物钟时间点，在麻醉雄性小鼠的视网膜和视丘脑中记录了视觉反应，并使用受体沉默替代方法选择性地刺激不同的光感受器类型。用旨在仅激活棒状的刺激，在主观夜晚中，中光范围内的反应具有高度的节律性，并且峰值幅度很大。在用玻璃体内注射间隙连接阻滞剂甲氯芬酸（meclofenamic acid）处理后，这种节律被消除了，这与光感受器之间电耦合强度的昼夜变化一致。相比之下，当适应背景辐照度时，在中光到光范围内，仅设计用于激活锥体的刺激的反应是无节律的。结果是，在整个生物钟白天，棒状加锥状的组合反应在中光-光背景下显示出稳定的对比度-反应关系，而在夜间，在较低的光水平下，反应明显放大。这些数据支持这样的观点，即生物钟是视觉的关键调节剂，在这种情况下，根据一天中的时间确定中光过渡中棒状/锥状视觉的相对幅度。尽管生物钟在调节视觉中的重要性早已被认识到，但对于生物钟如何在棒状和锥状均活跃的情况下塑造视觉（中光条件），人们知之甚少。在这里，应用了受体沉默替代的新颖方法来追踪小鼠在整个生物钟周期中的棒状和锥状视觉反应，并在棒状视觉中发现了明显的节律，而在锥状视觉中则没有。这会在夜间的较暗背景下增强反应，代价是在中光到光的范围内降低对比度-反应稳定性。因此，生物钟会促使棒状相对于锥状对视觉的相对贡献发生预期变化，从而与当前的视觉环境相匹配。
