Short Term Adaptations in Photoreceptors

描述（由申请人提供）：视网膜包含一种研究得最好的g蛋白偶联受体（GPCR），光激活的光导级联负责视觉感知。因此，它作为全身GPCR系统的模型，然而关于GPCR信号的反馈和调节仍然存在重要的未解问题，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，以适应环境光照的变化。这些分子事件被部分理解，但需要进一步的工作来确定适应的多种机制。本研究的第一个目标是确定引发杆状光感受器中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光感受器在接触强光后的一种矛盾的超敏反应。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。这项工作将揭示在中视光照条件下的视觉系统适应的新信息，每天两次的黄昏在进化上对猎人和猎物之间的联系至关重要。此外，我们的努力将提供一个更全面的了解如何修改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，但锥体光感受器对白天视觉，空间敏锐度和色彩感知具有巨大的重要性。在这一点上，对杆机制有了更好的理解，其中许多并不直接转化为锥函数。需要研究的一个重要方面是视锥细胞的巨大适应范围和它们完成任务的速度。事实上，视锥视觉的时间闪烁分辨率需要在单细胞水平上得到更详细的解释。对视锥细胞功能和适应的更全面的了解不仅将进一步促进视觉领域的发展，而且将进一步促进整个神经生物学领域对不同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.