Influence of light history on circadian photobiological responses

描述(申请人提供)：进入哺乳动物眼睛的光线激活一条独立于经典视觉系统的神经通路，用于调节昼夜节律。这种神经通路对光的反应随着环境的不同而不同，因此，非成像视觉系统代表了一个吸引人的神经可塑性模型系统。光周期的季节变化提供了一个丰富的例子，说明光历史如何显著改变光对昼夜节律的调节。具体地说，与相对较长的夏季白天相比，在较短的冬季类光周期之前夹带导致的最大相移大约大两倍(Goldman和Elliott，1988；Evans等人，2004)。尽管光周期的影响如此显著，但令人惊讶的是，对这些发现的后续行动很少。最近的初步工作证实了光周期对昼夜节律响应的影响，并进一步证明了先前处于短光周期的动物对相位推进的敏感性增加，进一步完善了我们对光周期如何调制光响应的理解。通过测试各种辐射范围内的昼夜节律输出，我们的目标是确定光周期历史是否影响阈值、灵敏度、增加速率和/或对光的最大反应。我们计划检测行为相移、褪黑素抑制和各种生化标志物，以最终确定先前的光历史调控昼夜节律输入的光敏感性的水平。将使用车轮运行活动节律来评估阶段，将通过光脉冲前后血浆水平的放射免疫分析来测量夜间褪黑素抑制，并将使用免疫细胞化学技术来确定在迄今进行的研究中观察到的行为敏感性差异的分子机制。一旦为每项研究收集了完整的数据，每组的通量-响应曲线将符合参数模型，将确定半饱和常数(即ED50)，ED50的显著差异将显示灵敏度的差异。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特殊后检验进行评估，并确定是否具有统计学意义。这些项目的结果应该有助于进一步阐明光历史调节昼夜节律的光的效力的神经机制。 公共卫生相关性：我们的目标是确定影响昼夜节律调节对光的敏感性的环境因素和神经机制。了解光敏感性是如何控制的，将有助于识别潜在的潜在生理异常，以及如何优化光疗来治疗情感障碍和昼夜睡眠障碍。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: We aim to determine the environmental factors and neural mechanisms that influence sensitivity to light for regulation of circadian rhythms. Understanding how light sensitivity is controlled will help to identify potential underlying physiological abnormalities as well as ways in which light therapy may be optimized for treatment of affective disorders and circadian sleep disturbances.