Influence of light history on circadian photobiological responses

光历史对昼夜光生物反应的影响

• 批准号: 8100368
• 负责人: Gena Glickman
• 金额: $ 3.31万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8100368
• 关键词: Animals; Behavioral; Biochemical Markers; Biological Models; Circadian Rhythms; Complement; Data; Dose; Environmental Risk Factor; Eye; FOS gene; Genes; Left; Light; Measures; Melatonin; Mesocricetus auratus; Modeling; Molecular; Mood Disorders; Neural Pathways; Neuronal Plasticity; Output; Pattern; Phase; Photons; Photoperiod; Photophobia; Phototherapy; Physiologic pulse; Physiological; Plasma; Proteins; Radioimmunoassay; Recording of previous events; Regulation; Relative (related person); Running; Series; Sleep disturbances; Techniques; Testing; Visual system structure; Work; abstracting; base; circadian pacemaker; follow-up; immunocytochemistry; molecular marker; neuromechanism; research study; response; suprachiasmatic nucleus

Project Summary/Abstract: Light entering the mammalian eye activates a neural pathway independent of the classical visual system, serving to regulate circadian rhythms. This neural pathway's response to light varies according to environmental context and thus, the non-image forming visual system represents an attractive model system of neural plasticity. Seasonal changes in photoperiod provide a rich example of how photic history can markedly change circadian regulation by light. Specifically, prior entrainment to a short winter-like photoperiod results in an approximately two-fold greater maximal phase shift as compared to relatively longer summer days (Goldman and Elliott, 1988; Evans et al., 2004). Despite this significant effect of photoperiod, surprisingly little has been done to follow-up on those findings. Recent preliminary work confirms the photoperiodic influence on circadian responsiveness and further demonstrates an increased sensitivity for phase advances in animals previously entrained to a short photoperiod, further refining our understanding of how photoperiod modulates photic response. By testing a variety of circadian outputs across a range of irradiances, we aim to determine whether photoperiodic history influences threshold, sensitivity, rate of increase, and/or maximal response to light. We plan to examine behavioral phase shifting, melatonin suppression and various biochemical markers in order to ultimately identify the level of regulation by which prior photic history modulates sensitivity to light for circadian input. Wheel-running activity rhythms will be employed to assess phase, nocturnal melatonin suppression will be measured via radioimmunoassay of pre- and post-light pulse plasma levels, and immunocytochemistry techniques will be used to identify the molecular mechanisms responsible for the behavioral differences in sensitivity observed in studies conducted thus far. Once a full complement of data have been collected for each study, fluence-response curves for each group will be fit to a parametric model, the half-saturation constant (i.e. ED50) will be determined, and significant differences in the ED50 will reveal differences in sensitivity. Data from each group will be analyzed via ANOVA, and statistical differences between groups will be assessed with post-hoc tests and determined significant if p<0.05. The results of these projects should serve to further elucidate the neural mechanisms by which photic history modulates the potency of light for circadian regulation.

项目摘要/摘要：进入哺乳动物眼睛的光会激活独立于经典视觉系统的神经通路，从而调节昼夜节律。这种神经通路对光的反应根据环境背景而变化，因此，非图像形成视觉系统代表了一种有吸引力的神经可塑性模型系统。光周期的季节性变化提供了一个丰富的例子，说明光历史如何显着改变光的昼夜节律调节。具体来说，与相对较长的夏季相比，先前进入类似冬季的短暂光周期会导致最大相移大约增加两倍（Goldman 和 Elliott，1988 年；Evans 等人，2004 年）。尽管光周期有如此显着的影响，但令人惊讶的是，对这些发现的后续研究却很少。最近的初步工作证实了光周期对昼夜节律反应的影响，并进一步证明了先前接受短光周期的动物对相位提前的敏感性增加，进一步完善了我们对光周期如何调节光反应的理解。通过测试一系列辐照度下的各种昼夜节律输出，我们的目的是确定光周期历史是否影响阈值、灵敏度、增加率和/或对光的最大反应。我们计划检查行为相移、褪黑激素抑制和各种生化标记物，以便最终确定先前的光历史调节昼夜节律输入对光的敏感性的调节水平。车轮运行活动节律将用于评估阶段，夜间褪黑激素抑制将通过光脉冲前和光脉冲后血浆水平的放射免疫测定来测量，免疫细胞化学技术将用于确定导致迄今为止进行的研究中观察到的敏感性行为差异的分子机制。一旦为每项研究收集了完整的数据，每组的注量响应曲线将适合参数模型，将确定半饱和常数（即 ED50），并且 ED50 的显着差异将揭示灵敏度的差异。每组的数据将通过方差分析进行分析，组间的统计差异将通过事后检验进行评估，如果 p<0.05，则确定显着性。这些项目的结果应有助于进一步阐明光历史调节光对昼夜节律的效力的神经机制。