Developmental and Translational Neurobiology Center, Virginia Tech Carilion Research Institute, Roanoke, VA, United States.
Graduate Program in Translational Biology, Medicine and Health, Virginia Tech, Blacksburg, VA, United States.
Front Neural Circuits. 2018 Feb 8;12:13. doi: 10.3389/fncir.2018.00013. eCollection 2018.
The suprachiasmatic nucleus (SCN) is the master pacemaker that drives circadian behaviors. SCN neurons have intrinsic, self-sustained rhythmicity that is governed by transcription-translation feedback loops. Intrinsic rhythms within the SCN do not match the day-night cycle and are therefore entrained by light-derived cues. Such cues are transmitted to the SCN by a class of intrinsically photosensitive retinal ganglion cells (ipRGCs). In the present study, we sought to identify how axons from ipRGCs target the SCN. While none of the potential targeting cues identified appeared necessary for retinohypothalamic innervation, we unexpectedly identified a novel role for the extracellular matrix protein F-spondin in circadian behavior. In the absence of F-spondin, mice lost their ability to maintain typical intrinsic rhythmicity. Moreover, F-spondin loss results in the displacement of vasoactive intestinal peptide (VIP)-expressing neurons, a class of neurons that are essential for maintaining rhythmicity among SCN neurons. Thus, this study highlights a novel role for F-spondin in maintaining circadian rhythms.
视交叉上核（SCN）是驱动昼夜节律行为的主起搏器。SCN 神经元具有内在的、自我维持的节律性，由转录-翻译反馈环控制。SCN 内的内在节律与昼夜周期不匹配，因此被光衍生的线索所调节。这些线索通过一类内在光敏性视网膜神经节细胞（ipRGCs）传递到 SCN。在本研究中，我们试图确定 ipRGCs 的轴突如何靶向 SCN。虽然确定的潜在靶向线索中没有一个对视网膜下丘脑传入是必需的，但我们出人意料地发现细胞外基质蛋白 F-spondin 在昼夜节律行为中具有新的作用。在缺乏 F-spondin 的情况下，小鼠失去了维持典型内在节律性的能力。此外，F-spondin 的缺失导致血管活性肠肽（VIP）表达神经元的移位，这类神经元对于维持 SCN 神经元之间的节律性至关重要。因此，这项研究强调了 F-spondin 在维持昼夜节律中的新作用。
