Cellular Neurobiology Research Unit, Institut de Recherches Cliniques de Montréal, Montréal, QC, Canada; Integrated Program in Neuroscience, McGill University, Montréal, QC, Canada.
Department of Biology, University of Akron, Akron, OH, USA.
Cell Rep. 2018 May 22;23(8):2416-2428. doi: 10.1016/j.celrep.2018.04.086.
Newborn neurons follow molecular cues to reach their final destination, but whether early life experience influences lamination remains largely unexplored. As light is among the first stimuli to reach the developing nervous system via intrinsically photosensitive retinal ganglion cells (ipRGCs), we asked whether ipRGCs could affect lamination in the developing mouse retina. We show here that ablation of ipRGCs causes cone photoreceptors to mislocalize at different apicobasal positions in the retina. This effect is partly mediated by light-evoked activity in ipRGCs, as dark rearing or silencing of ipRGCs leads a subset of cones to mislocalize. Furthermore, ablation of ipRGCs alters the cone transcriptome and decreases expression of the dopamine receptor D4, while injection of L-DOPA or D4 receptor agonist rescues the displaced cone phenotype observed in dark-reared animals. These results show that early light-mediated activity in ipRGCs influences neuronal lamination and identify ipRGC-elicited dopamine release as a mechanism influencing cone position.
新生神经元会根据分子线索到达最终目的地，但早期生活经验是否会影响分层仍在很大程度上尚未得到探索。由于光作为最早通过内在光敏视网膜神经节细胞（ipRGCs）到达发育中神经系统的刺激之一，我们想知道 ipRGCs 是否会影响发育中的小鼠视网膜的分层。我们在这里表明，ipRGCs 的消融会导致视锥细胞在视网膜的不同顶底位置发生错误定位。这种效应部分是由 ipRGCs 中的光诱发活动介导的，因为暗饲养或 ipRGCs 的沉默会导致一部分视锥细胞发生错误定位。此外，ipRGCs 的消融会改变视锥细胞的转录组并降低多巴胺受体 D4 的表达，而 L-DOPA 或 D4 受体激动剂的注射可挽救在暗饲养动物中观察到的移位视锥细胞表型。这些结果表明，ipRGCs 中的早期光介导活动会影响神经元的分层，并确定由 ipRGC 引发的多巴胺释放是影响视锥细胞位置的一种机制。
