REGULATION OF CIRCADIAN PHYSIOLOGY AND BEHAVIOR

哺乳动物昼夜节律系统的组织正受到关注 在下丘脑的水平，然而， 这些下丘脑中心仍然是未知的。 我们最近关于视网膜的数据 退化（RD/RD）小鼠，表明昼夜行为正常 由少数缺乏外节的锥体调节， 或者，哺乳动物中的一类新型光感受细胞， 视网膜不受RD/RD突变的影响。 在这些研究中，我们 利用经历杆快速丢失的RD/RD小鼠 光感受器随后是更持久的视锥细胞损失。 我们 实验提出： 1)将对光线的昼夜行为反应与存在或 视网膜杆和锥的缺失。a）我们将比较光谱 RD/RD和+/+小鼠中昼夜节律反应的敏感性。 是光谱 敏感性是杆状还是锥形？B）昼夜光敏感性是否在rd/rd 小鼠平行光感受器胞体的损失？c）辐照度 在rd/rd中相同的夹带至全光周期所需的水平， +/+小鼠？ 2)识别哺乳动物体内的昼夜光感受元件 视网膜。 具体来说，我们的目标是解决昼夜光检测是否 可以归因于视杆细胞、视锥细胞或两者都不是。 （a）的类型和地点 RD/RD小鼠视网膜内剩余的光感受器将被 使用视蛋白抗体、视蛋白信息探针和 视觉色素发色团11-顺式-视黄醇的定量。B） 11-顺式-视黄醛与细胞色素介导的相互作用 将使用11-顺式锁定视网膜光检测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。 视杆细胞和视锥细胞 松果体褪黑激素合成 我们将比较抑制的灵敏度 rd/rd、rds/rds和+/+基因型光刺激对褪黑素的影响。 人体昼夜生理的扰动（时差，轮班工作疲劳， 季节性情感障碍）具有短暂但深刻的负面影响 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.