Short Term Adaptations in Photoreceptors

描述(申请人提供)：视网膜含有研究最深入的G蛋白偶联受体(GPCR)之一，它是负责视觉感知的光激活光转导通路。因此，它可以作为全身GPCR系统的模型，但关于GPCR信号的反馈和调制仍然存在重要的悬而未决的问题，特别是当它影响级联的终止时。可靠的关闭在光感受器中受到高度控制，它建立了视觉系统的时间能力。更重要的是，光感受器可以改变关闭时间，以适应环境照明的变化。这些分子事件在一定程度上是可以理解的，但还需要进一步的工作来定义适应的多种机制。这项拟议研究的第一个目标是确定在杆状感光细胞中引发一种新发现的适应形式的条件，并确定控制它的潜在机制。这种形式的适应揭示了我们的暗光感光细胞在暴露在强光下后的一种矛盾的超敏反应。我们建议在细胞水平以及通过人类受试者的临床和行为测试来研究这种杆状适应。这项工作将揭示关于中间视觉照明条件下视觉系统适应的新信息，中间视觉照明条件下一天两次的黄昏对于机器人猎人和被猎人来说是至关重要的。此外，我们的努力将提供一个更全面的理解，如何修改GPCR途径，以适应持续的刺激。尽管视锥感受器是人类视觉系统中的少数细胞，但它对白天的视觉、空间敏锐度和颜色感知都具有极其重要的作用。在这一点上，对杆机构有了更好的理解，其中许多机构并不能直接转化为圆锥函数。需要研究的一个重要方面是锥体的巨大适应范围和它们完成任务的速度。事实上，需要在单细胞水平上更详细地解释从行为上测量的视锥视觉的时间闪烁分辨率。更全面地了解视锥细胞的功能和适应，不仅将促进视野，而且将促进神经生物学的整个领域与不同的GPCR信号通路。

DESCRIPTION (provided by applicant): The retina contains one of the best-studied G-protein coupled receptors (GPCR), the light-activated phototransduction cascade responsible for visual perception. As such it serves as a model for GPCR systems throughout the body, and yet there remain important unanswered questions about the feedback and modulation of GPCR signaling, especially as it affects termination of the cascade. The reliable shutoff is highly controlled in photoreceptors, and it establishes the temporal capabilities of the visual system. More importantly, photoreceptors can alter shutoff timing as an adaptation to changes in ambient illumination. These molecular events are understood in part, but further work is required to define the multiple mechanisms of adaptation. The first goal of this proposed research is to identify the conditions that elicit a newly discovered form of adaptation in rod photoreceptors and to ascertain the underlying mechanisms controlling it. This form of adaptation reveals a paradoxical hypersensitivity of our dim light photoreceptors following exposure to bright light. We propose to study this rod adaptation at cellular level as well as through clinical and behavioral tests in human subjects. This work will reveal new information about visual system adaptation during mesopic lighting conditions, the twice-daily twilight evolutionarily vital to bot the hunter and the hunted. Additionally, our efforts will provide a more thorough understanding of how the GPCR pathway can be modified to adapt to constant stimuli. Despite being the minority cell in the human visual system, cone photoreceptors have tremendous importance for daytime vision, spatial acuity, and color perception. At this point, there is a far better understanding of rod mechanisms, many of which do not directly translate to cone function. One important aspect that needs to be investigated is the immense adaptive range of cones and the speed with which they accomplish the task. Indeed, the temporal flicker resolution of cone vision measured behaviorally needs to be explained in more detail on the single cell level. A more complete understanding of cone function and adaptation will further not only the field of vision, but the entire field of neurobiology with respect to different GPCR signaling pathways.