REGULATION OF PHOTORECEPTORS SPECTRAL SENSITIVITY

这些研究的目的是阐明决定 单个感光细胞的光谱灵敏度。总的来说， 光感受器的光谱灵敏度将取决于 视色素的表达和色素的吸收特性。 这两个方面都没有得到很好的理解。一种视觉色素 光谱调谐是由发色团的微扰产生的， 特异性视蛋白本建议的第一个目的是找出如何和 其中视蛋白扰动发色团以调节其吸收。我 方法将是表征分离的光谱灵敏度 电生理学之前蝾螈和金鱼的杆和锥 并且在用化学修饰的 视网膜类似物。使用一系列二氢视网膜类似物，我们将 定位与视蛋白相互作用的发色位点。第二 目的是发现细胞是否可以表达多种视蛋白， 是否所有的视蛋白都能形成功能性色素。虽然一个人 光感受器被认为只表达一种类型的视蛋白， 有证据表明有些光感受器违反了这一规则。我们将 测试豚鼠视锥细胞中两种功能性视蛋白的存在， 通过测量细胞的光谱灵敏度， 在暴露于强烈的漂白光之前和之后。光谱 漂白光的成分将被仔细选择， 颜料类型优先漂白。进一步证明 表达的多种视蛋白将使用 免疫组织化学和分子生物学探针。第三个目标是 研究光感受器改变类型的能力 它们表达的视蛋白。我们将测量视锥细胞的光谱灵敏度 在不同年龄的蝾螈和冬比目鱼中， 颜料含量作为时间的函数而变化。的结果予以 研究可能对调节 视锥密度和视锥特异性神经回路的形成 视网膜。这些研究的长期目标是了解 视网膜编码由波长携带的视觉信息， 潜在机制的可塑性。

The goal of these studies is to elucidate factors that determine the spectral sensitivities of individual photoreceptor cells. In general, a photoreceptor's spectral sensitivity will depend upon the type of visual pigment expressed and the absorption properties of the pigment. Neither of these aspects is well understood. A visual pigment's spectral tuning is produced by perturbations of the chromophore by its specific opsin. The first aim of this proposal is to find out how and where opsin perturbs the chromophore to tune its absorption. My approach will be to characterize the spectral sensitivities of isolated rods and cones of salamander and goldfish electrophysiologically before and after replacing their native chromophore with chemically modified retinal analogs. Using a series of dihydroretinal analogs, we will localize the chromophoric sites that interact with opsin. The second aim is to find out whether a cell can express multiple opsins and whether all opsins form functional pigments. Although an individual photoreceptor is thought to express only one type of opsin, there is evidence to suggest that some photoreceptors violate this rule. We will test for the presence of two functional opsins in guinea pig cones and three in salamander cones by measuring the cell's spectral sensitivity before and after exposure to an intense bleaching light. The spectral composition of the bleaching light will be carefully chosen so that one pigment type is bleached preferentially. Additional evidence that multiple opsins are expressed will be obtained using immunohistochemical and molecular biological probes. The third aim is to investigate the ability of photoreceptors to change the type of opsin they express. We will measure the spectral sensitivities of cones in salamander and winter flounder at different ages to see if their pigment content changes as a function of time. The results of these studies could have developmental significance for the regulation of cone density and the formation of cone-specific neural circuits in the retina. The long term goal of these studies is to understand how the retina encodes visual information carried by wavelength and to explore the plasticity of the underlying mechanisms.