Program in Neuroscience and Behavior, University of Massachusetts, Amherst, Massachusetts.
Department of Biology, University of Massachusetts, Amherst, Massachusetts.
Eur J Neurosci. 2018 Dec;48(11):3319-3334. doi: 10.1111/ejn.14214.
Mammalian circadian rhythms are entrained by photic stimuli that are relayed by retinal projections to the core of the suprachiasmatic nucleus (SCN). Neuronal activation, as demonstrated by expression of the immediate early gene c-fos, leads to transcription of the core clock gene per1. The duper mutation in hamsters shortens circadian period and amplifies light-induced phase shifts. We performed two experiments to compare the number of c-FOS immunoreactive (ir) and PER1-ir cells, and the intensity of staining, in the SCN of wild-type (WT) and duper hamsters at various intervals after presentation of a 15-min light pulse in the early subjective night. Light-induced c-FOS-ir within 1 hr in the dorsocaudal SCN of duper, but not WT hamsters. In cells that express vasoactive intestinal peptide (VIP), which plays a critical role in synchronization of SCN cellular oscillators, light-induced c-FOS-ir was greater in duper than WT hamsters. After the light pulse, PER1-ir cells were found in more medial portions of the SCN than FOS-ir, and appeared with a longer latency and over a longer time course, in VIP cells of duper than wild-type hamsters. Our results indicate that the duper allele alters SCN function in ways that may contribute to changes in free running period and phase resetting.
哺乳动物的昼夜节律受光刺激的影响,这些光刺激通过视网膜投射到视交叉上核(SCN)的核心。神经元的激活,如即时早期基因 c-fos 的表达所示,导致核心时钟基因 per1 的转录。仓鼠中的 duper 突变缩短了昼夜周期并放大了光诱导的相位移动。我们进行了两项实验,比较了在早期主观夜间呈现 15 分钟光脉冲后,不同时间间隔下野生型(WT)和 duper 仓鼠 SCN 中的 c-FOS 免疫反应(ir)和 PER1-ir 细胞的数量和染色强度。在 dorsocaudal SCN 中,duper 但不是 WT 仓鼠中的 c-FOS-ir 在 1 小时内光诱导。在表达血管活性肠肽(VIP)的细胞中,VIP 在 SCN 细胞振荡器的同步中起着关键作用,在 duper 比 WT 仓鼠中的 c-FOS-ir 更大。在光脉冲之后,PER1-ir 细胞出现在 SCN 的更内侧部分,而不是 FOS-ir,并且在 VIP 细胞中,duper 比野生型仓鼠的潜伏期更长,持续时间更长。我们的结果表明,duper 等位基因以可能导致自由运行周期和相位重置变化的方式改变 SCN 功能。