Short Term Adaptations in Photoreceptors

描述（由申请人提供）：视网膜含有研究最多的G蛋白偶联受体（GPCR）之一，即负责视觉感知的光激活光转导级联。因此，它作为全身GPCR系统的模型，但仍然存在关于GPCR信号传导的反馈和调节的重要未回答的问题，特别是因为它影响级联的终止。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。这些分子事件被部分理解，但需要进一步的工作来定义适应的多种机制。这项研究的第一个目标是确定条件，引起一个新发现的形式的适应杆光感受器，并确定其控制的潜在机制。这种形式的适应揭示了一个矛盾的超敏反应，我们的昏暗的光感受器暴露在明亮的光。我们建议在细胞水平上以及通过人类受试者的临床和行为测试来研究这种杆适应。这项工作将揭示有关视觉系统在中间视觉照明条件下适应的新信息，每天两次的黄昏对猎人和猎物至关重要。此外，我们的努力将使人们更深入地了解如何修饰GPCR途径以适应持续的刺激。尽管是人类视觉系统中的少数细胞，但锥状光感受器对于白天视觉、空间敏锐度和颜色感知具有巨大的重要性。在这一点上，有一个更好的理解杆机制，其中许多不直接转化为锥功能。需要研究的一个重要方面是锥体的巨大适应范围以及它们完成任务的速度。事实上，时间闪烁分辨率的锥视觉测量行为需要在单细胞水平上更详细地解释。更全面地了解视锥细胞的功能和适应性不仅将进一步扩大视野，而且将进一步扩大整个神经生物学领域关于不同GPCR信号通路的研究。

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.