Department of Ophthalmology & Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.
Department of Molecular, Cellular & Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
Vis Neurosci. 2021 Sep 16;38:E014. doi: 10.1017/S0952523821000134.
Intrinsically photosensitive retinal ganglion cells (ipRGCs) signal not only anterogradely to drive behavioral responses, but also retrogradely to some amacrine interneurons to modulate retinal physiology. We previously found that all displaced amacrine cells with spiking, tonic excitatory photoresponses receive gap-junction input from ipRGCs, but the connectivity patterns and functional roles of ipRGC-amacrine coupling remained largely unknown. Here, we injected PoPro1 fluorescent tracer into all six types of mouse ipRGCs to identify coupled amacrine cells, and analyzed the latter's morphological and electrophysiological properties. We also examined how genetically disrupting ipRGC-amacrine coupling affected ipRGC photoresponses. Results showed that ipRGCs couple with not just ON- and ON/OFF-stratified amacrine cells in the ganglion-cell layer as previously reported, but also OFF-stratified amacrine cells in both ganglion-cell and inner nuclear layers. M1- and M3-type ipRGCs couple mainly with ON/OFF-stratified amacrine cells, whereas the other ipRGC types couple almost exclusively with ON-stratified ones. ipRGCs transmit melanopsin-based light responses to at least 93% of the coupled amacrine cells. Some of the ON-stratifying ipRGC-coupled amacrine cells exhibit transient hyperpolarizing light responses. We detected bidirectional electrical transmission between an ipRGC and a coupled amacrine cell, although transmission was asymmetric for this particular cell pair, favoring the ipRGC-to-amacrine direction. We also observed electrical transmission between two amacrine cells coupled to the same ipRGC. In both scenarios of coupling, the coupled cells often spiked synchronously. While ipRGC-amacrine coupling somewhat reduces the peak firing rates of ipRGCs' intrinsic melanopsin-based photoresponses, it renders these responses more sustained and longer-lasting. In summary, ipRGCs' gap junctional network involves more amacrine cell types and plays more roles than previously appreciated.
内在光敏视网膜神经节细胞（ipRGCs）不仅向前传递信号以驱动行为反应，而且向后传递信号至某些无长突细胞（amacrine interneurons）以调节视网膜生理学。我们之前发现，所有具有放电、紧张性兴奋性光反应的离散型无长突细胞均从 ipRGC 接收缝隙连接输入，但 ipRGC-无长突细胞连接的连接模式和功能作用在很大程度上仍不清楚。在这里，我们将 PoPro1 荧光示踪剂注入所有六种类型的小鼠 ipRGC 中以鉴定偶联的无长突细胞，并分析后者的形态和电生理特性。我们还研究了遗传破坏 ipRGC-无长突细胞偶联如何影响 ipRGC 光反应。结果表明，ipRGC 不仅与以前报道的神经节细胞层中的 ON-和 ON/OFF 分层无长突细胞，而且还与神经节细胞层和内核层中的 OFF 分层无长突细胞偶联。M1-和 M3 型 ipRGC 主要与 ON/OFF 分层无长突细胞偶联，而其他 ipRGC 类型几乎仅与 ON 分层无长突细胞偶联。ipRGC 将黑视素基光反应传递至至少 93%的偶联无长突细胞。一些 ON 分层 ipRGC 偶联的无长突细胞表现出短暂的超极化光反应。我们在 ipRGC 和偶联的无长突细胞之间检测到双向电传递，尽管对于这个特定的细胞对，传递是不对称的，有利于 ipRGC 到无长突细胞的方向。我们还观察到偶联至同一 ipRGC 的两个无长突细胞之间的电传递。在这两种偶联情况下，偶联细胞通常同步放电。虽然 ipRGC-无长突细胞偶联略微降低了 ipRGC 内在黑视素基光反应的峰值放电率，但使这些反应更持久和更持久。总之，ipRGC 的缝隙连接网络涉及比以前预期更多的无长突细胞类型并发挥更多作用。
