Centre for Biological Timing, Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK.
Division of Diabetes, Endocrinology and Gastroenterology, Faculty of Biology Medicine and Health, University of Manchester, Manchester, UK.
J Pineal Res. 2021 May;70(4):e12735. doi: 10.1111/jpi.12735.
Intrinsically photosensitive retinal ganglion cells convey intrinsic, melanopsin-based, photoreceptive signals alongside those produced by rods and cones to the suprachiasmatic nucleus (SCN) circadian clock. To date, experimental data suggest that melanopsin plays a more significant role in measuring ambient light intensity than cone photoreception. Such studies have overwhelmingly used diffuse light stimuli, whereas light intensity in the world around us varies across space and time. Here, we investigated the extent to which melanopsin or cone signals support circadian irradiance measurements in the presence of naturalistic spatiotemporal variations in light intensity. To address this, we first presented high- and low-contrast movies to anaesthetised mice whilst recording extracellular electrophysiological activity from the SCN. Using a mouse line with altered cone sensitivity (Opn1mw mice) and multispectral light sources we then selectively varied irradiance of the movies for specific photoreceptor classes. We found that steps in melanopic irradiance largely account for the light induced-changes in SCN activity over a range of starting light intensities and in the presence of spatiotemporal modulation. By contrast, cone-directed changes in irradiance only influenced SCN activity when spatiotemporal contrast was low. Consistent with these findings, under housing conditions where we could independently adjust irradiance for melanopsin versus cones, the period lengthening effects of constant light on circadian rhythms in behaviour were reliably determined by melanopic irradiance, regardless of irradiance for cones. These data add to the growing evidence that modulating effective irradiance for melanopsin is an effective strategy for controlling the circadian impact of light.
内在光敏视网膜神经节细胞将内在的、基于黑视蛋白的光感受信号与视杆细胞和视锥细胞产生的信号一起传递到视交叉上核(SCN)生物钟。迄今为止,实验数据表明,黑视蛋白在测量环境光强方面比视锥细胞感光发挥更重要的作用。这些研究 overwhelmingly 使用漫射光刺激,而我们周围的光强度在空间和时间上都在变化。在这里,我们研究了在光强度具有自然时空变化的情况下,黑视蛋白或视锥细胞信号在多大程度上支持生物钟辐照度测量。为了解决这个问题,我们首先向麻醉小鼠呈现高对比度和低对比度电影,同时记录 SCN 的细胞外电生理活动。使用具有改变的视锥细胞敏感性的小鼠系(Opn1mw 小鼠)和多光谱光源,我们然后选择性地改变电影的辐照度,用于特定的光感受器类。我们发现,在一系列起始光强度下,以及在存在时空调制的情况下,黑视蛋白辐照度的阶跃在很大程度上解释了 SCN 活动的光诱导变化。相比之下,只有在时空对比度低时,视锥细胞定向的辐照度变化才会影响 SCN 活动。这些发现与我们的发现一致,即在我们可以独立调节黑视蛋白和视锥细胞的辐照度的居住条件下,恒定光对行为节律的生物钟延长作用可靠地由黑视蛋白辐照度决定,而与视锥细胞的辐照度无关。这些数据增加了越来越多的证据表明,调节黑视蛋白的有效辐照度是控制光对生物钟影响的有效策略。