Reifler Aaron N, Chervenak Andrew P, Dolikian Michael E, Benenati Brian A, Meyers Benjamin S, Demertzis Zachary D, Lynch Andrew M, Li Benjamin Y, Wachter Rebecca D, Abufarha Fady S, Dulka Eden A, Pack Weston, Zhao Xiwu, Wong Kwoon Y
Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA.
Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA; Department of Molecular, Cellular & Developmental Biology, University of Michigan, Ann Arbor, MI 48105, USA.
Exp Eye Res. 2015 Jan;130:17-28. doi: 10.1016/j.exer.2014.11.010. Epub 2014 Nov 18.
Intrinsically photosensitive retinal ganglion cells (ipRGCs) are inner retinal photoreceptors that mediate non-image-forming visual functions, e.g. pupillary constriction, regulation of pineal melatonin release, and circadian photoentrainment. Five types of ipRGCs were recently discovered in mouse, but whether they exist in other mammals remained unknown. We report that the rat also has five types of ipRGCs, whose morphologies match those of mouse ipRGCs; this is the first demonstration of all five cell types in a non-mouse species. Through immunostaining and λmax measurements, we showed that melanopsin is likely the photopigment of all rat ipRGCs. The various cell types exhibited diverse spontaneous spike rates, with the M1 type spiking the least and M4 spiking the most, just like we had observed for their mouse counterparts. Also similar to mouse, all ipRGCs in rat generated not only sluggish intrinsic photoresponses but also fast, synaptically driven ones. However, we noticed two significant differences between these species. First, whereas we learned previously that all mouse ipRGCs had equally sustained synaptic light responses, rat M1 cells' synaptic photoresponses were far more transient than those of M2-M5. Since M1 cells provide all input to the circadian clock, this rat-versus-mouse discrepancy could explain the difference in photoentrainment threshold between mouse and other species. Second, rat ipRGCs' melanopsin-based spiking photoresponses could be classified into three varieties, but only two were discerned for mouse ipRGCs. This correlation of spiking photoresponses with cell types will help researchers classify ipRGCs in multielectrode-array (MEA) spike recordings.
内在光敏性视网膜神经节细胞（ipRGCs）是视网膜内层的光感受器，介导非成像视觉功能，如瞳孔收缩、松果体褪黑素释放的调节以及昼夜节律的光同步化。最近在小鼠中发现了五种类型的ipRGCs，但它们是否存在于其他哺乳动物中仍不清楚。我们报告大鼠也有五种类型的ipRGCs，其形态与小鼠的ipRGCs相匹配；这是在非小鼠物种中首次证明所有五种细胞类型的存在。通过免疫染色和最大吸收波长测量，我们表明黑视蛋白可能是所有大鼠ipRGCs的光色素。各种细胞类型表现出不同的自发放电率，M1型放电最少，M4型放电最多，就像我们在它们的小鼠对应物中观察到的那样。同样与小鼠相似，大鼠中的所有ipRGCs不仅产生缓慢的内在光反应，还产生快速的、由突触驱动的光反应。然而，我们注意到这些物种之间有两个显著差异。首先，虽然我们之前了解到所有小鼠ipRGCs都有同样持续的突触光反应，但大鼠M1细胞的突触光反应比M2 - M5细胞的突触光反应更短暂。由于M1细胞为昼夜节律时钟提供所有输入，这种大鼠与小鼠的差异可以解释小鼠与其他物种之间光同步化阈值的差异。其次，大鼠ipRGCs基于黑视蛋白的放电光反应可分为三种类型，但在小鼠ipRGCs中只识别出两种。这种放电光反应与细胞类型的相关性将有助于研究人员在多电极阵列（MEA）放电记录中对ipRGCs进行分类。
