Abstract：
Seasonal daylength, or circadian photoperiod, is a pervasive environmental signal that profoundly influences physiology and behavior. In mammals, the central circadian clock resides in the suprachiasmatic nuclei (SCN) of the hypothalamus where it receives retinal input and synchronizes, or entrains, organismal physiology and behavior to the prevailing light cycle. The process of entrainment induces sustained plasticity in the SCN, but the molecular mechanisms underlying SCN plasticity are incompletely understood. Entrainment to different photoperiods persistently alters the timing, waveform, period, and light resetting properties of the SCN clock and its driven rhythms. To elucidate novel candidate genes for molecular mechanisms of photoperiod plasticity, we performed RNA sequencing on whole SCN dissected from mice raised in long (light:dark [LD] 16:8) and short (LD 8:16) photoperiods. Fewer rhythmic genes were detected in mice subjected to long photoperiod, and in general, the timing of gene expression rhythms was advanced 4-6 h. However, a few genes showed significant delays, including Gem. There were significant changes in the expression of the clock-associated gene Timeless and in SCN genes related to light responses, neuropeptides, gamma aminobutyric acid (GABA), ion channels, and serotonin. Particularly striking were differences in the expression of the neuropeptide signaling genes Prokr2 and Cck, as well as convergent regulation of the expression of 3 SCN light response genes, Dusp4, Rasd1, and Gem. Transcriptional modulation of Dusp4 and Rasd1 and phase regulation of Gem are compelling candidate molecular mechanisms for plasticity in the SCN light response through their modulation of the critical NMDAR-MAPK/ERK-CREB/CRE light signaling pathway in SCN neurons. Modulation of Prokr2 and Cck may critically support SCN neural network reconfiguration during photoperiodic entrainment. Our findings identify the SCN light response and neuropeptide signaling gene sets as rich substrates for elucidating novel mechanisms of photoperiod plasticity. Data are also available at http://circadianphotoperiodseq.com/, where users can view the expression and rhythmic properties of genes across these photoperiod conditions.
摘要：
季节性日长，或者昼夜节律光周期，是一种普遍的环境信号，深刻地影响着生理和行为。在哺乳动物中,中央生物钟位于下丘脑的视交叉上核（SCN），在那里它接收视网膜输入并同步，或夹带物，对普遍光周期的有机体生理和行为。夹带过程诱导SCN持续可塑性，但SCN可塑性的分子机制尚不完全清楚。不同光周期的夹带会持续改变时机，波形,period,以及SCN时钟及其驱动节奏的光复位特性。为了阐明光周期可塑性分子机制的新候选基因，我们对从长（亮：暗[LD]16:8）和短（LD8:16）光周期饲养的小鼠解剖的整个SCN进行了RNA测序。在经历长光周期的小鼠中检测到较少的节律基因，总的来说,基因表达节律的时间提前4-6小时。然而，一些基因显示出明显的延迟，包括宝石.时钟相关基因Timeless和与光反应相关的SCN基因的表达有显著变化，神经肽，γ-氨基丁酸(GABA),离子通道,还有血清素.特别引人注目的是神经肽信号基因Prokr2和Cck的表达差异，以及3个SCN光响应基因表达的趋同调控，Dusp4，Rasd1和宝石。Dusp4和Rasd1的转录调节和Gem的相位调节是通过调节SCN神经元中关键的NMDAR-MAPK/ERK-CREB/CRE光信号通路在SCN光响应中可塑性的令人信服的候选分子机制。Prokr2和Cck的调制可能会在光周期夹带过程中严重支持SCN神经网络的重新配置。我们的发现将SCN光响应和神经肽信号传导基因集确定为阐明光周期可塑性新机制的丰富底物。数据也可在http://circadianphotoperiodseq.com/，用户可以在这些光周期条件下查看基因的表达和节律特性。
