REGULATION OF CIRCADIAN PHYSIOLOGY AND BEHAVIOR

哺乳动物昼夜节律系统的组织正在受到关注 在下丘脑的水平上，但调节 这些下丘脑中心仍然未知。我们关于视网膜的最新数据 退化(RD/RD)小鼠，表明昼夜节律行为正常 由少数没有外部节段的圆锥体或 或者，哺乳动物中一类新的感光细胞 不受RD/RD突变影响的视网膜。在这些研究中，我们 利用快速失去杆子的RD/RD小鼠 光感受器紧随其后的是更持久的锥体细胞丢失。我们的 实验建议： 1)将昼夜节律对光的行为反应与存在或 无视网膜视杆和视锥细胞。A)我们将比较光谱 RD/RD和+/+小鼠昼夜节律反应的敏感性。是光谱 感光棒状还是锥状？B)Rd/Rd的昼夜节律光敏性 小鼠的光感受器周围的丢失？C)是辐照度 卷吸到全光周期所需的水平在RD/RD和 +/+老鼠？ 2)确定哺乳动物体内的昼夜节律感光元件 视网膜。具体地说，我们的目标是解决昼夜节律光检测 可以归因于杆状、圆锥状或两者都不是。A)项目的类型和地点 RD/RD小鼠视网膜内剩余的光感受器将是 使用视蛋白抗体、视蛋白信息的探针和 视觉色素发色团11-顺式视黄醛的定量。b) 11-顺式视黄醛与光敏色素之间的联系 将使用11顺式锁定的视网膜建立昼夜节律光检测 类似物和SDS-PAGE分析。 3)比较调节昼夜节律反应的光感受器和 调节松果体生理的光感受器。视杆和视锥调节吗？ 松果体褪黑激素合成？我们将比较压制的敏感性 Rd/Rd、Rds/Rds和+/+三种基因型光对褪黑素的影响。 人体昼夜节律生理的扰动(时差、轮班工作疲劳、 季节性情感障碍)有短暂但深远的负面影响 关于个人健康。更好地了解哺乳动物的昼夜节律 系统，特别是它们的光调节，将提供急需的 关于生物学和人类健康这一复杂领域的信息。

The organization of the mammalian circadian system is receiving attention at the level of the hypothalamus, yet the photoreceptors that regulate these hypothalamic centers remain unknown. Our recent data on retinally degenerate (rd/rd) mice, suggest that circadian behavior is normally regulated by either a small number of cones which lack outer segments or alternatively, a novel class of photoreceptive cells in the mammalian retina which is unaffected by the rd/rd mutation. In these studies we utilize the rd/rd mouse which experiences a rapid loss of rod photoreceptors followed by a more protracted loss of cone cells. Our experiments propose to: 1) Correlate circadian behavioral responses to light with the presence or absence of retinal rods and cones. a) We will compare the spectral sensitivity of circadian responses in rd/rd and +/+ mice. Is the spectral sensitivity rod- or cone-like? b) Does circadian photosensitivity in rd/rd mice parallel the loss of photoreceptor perikarya? c) Are the irradiance levels required for entrainment to full photoperiods the same in rd/rd and +/+ mice? 2) Identify the circadian photoreceptive elements within the mammalian retina. Specifically, we aim to address whether circadian light detection can be attributed to rods, cones or neither. a) The type and location of the remaining photoreceptors within the retina of rd/rd mice will be determined using opsin antibodies, probes to opsin message, and quantification of the visual pigment chromophore 11-cis-retinaldehyde. b) The link between 11-cis-retinaldehyde and the photopigment mediating circadian light detection will be established using 11-cis-locked retinal analogs and SDS-PAGE analysis. 3) Compare the photoreceptors that regulate circadian responses and the photoreceptors that regulate pineal physiology. Do rods and cones regulate pineal melatonin synthesis? We will compare the sensitivity of suppression of melatonin by light in rd/rd, rds/rds and +/+ genotypes. Perturbation of human circadian physiology (jet-lag, shift-work fatigue, seasonal affective disorder) has transient but profoundly negative effects on individual health. A better understanding of mammalian circadian systems and specifically their regulation by light will provide much needed information on this complex area of biology and human health.