Functional characteristics of rod pathways in the retina

视网膜视杆细胞通路的功能特征

• 批准号: 8790366
• 负责人: Alapakkam P Sampath
• 金额: $ 26.05万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-08 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8790366
• 关键词: Functional; characteristics; rod; pathways; retina

DESCRIPTION (provided by applicant): Rod vision in mammals is remarkably sensitive, allowing vision under conditions where few rods absorb photons. Additionally, rod vision extends over 8 orders of magnitude in light intensity above this threshold. The experiments described in this proposal are aimed at elucidating fundamental retinal mechanisms that allow both the discrimination of rod photoresponses from noise near visual threshold, and allow rod photoresponses to be transmitted to retinal ganglion cells through several parallel pathways over a wide range of light intensities. To accomplish these goals we propose to record light-evoked responses from rod photoreceptors and downstream retinal neurons (bipolar cells, amacrine cells, and ganglion cells) of wild-type and several transgenic mouse strains. We aim to answer several fundamental questions about how rod photoresponses are processed and parsed within the retinal circuitry. First, we propose to identify the limiting source of noise in the rod photoreceptors that sets visual threshold by utilizing mouse models with reduced rod noise. We will compare how reduced noise influences the detection of single photon responses, and how it influences the behavioral threshold for seeing. The limiting noise in rods reflects a key control point within rod phototransduction that sets absolute visual threshold. Second, we propose to characterize the properties of rod-driven signals in the primary rod pathway and determine how sensitivity is modulated during adaptation to background light. Finally, we propose to characterize how cone bipolar cells integrate rod-driven signals generated by the primary and secondary rod pathways, along with cone-driven signals, using mice where either rod or cone phototransduction has been silenced. These experiments will allow us to dissect how rod-driven signals in many parallel pathways combine with cone-driven signals to define the dynamic range of rod vision. Our long-term goal is to provide a comprehensive understanding of the mechanisms that control the transmission of rod-driven signals to higher visual centers. This work is aligned with the objectives of the Retinal Diseases Program of the NEI "to use molecular and physiological approaches to identify post photoreceptor neural components of adaptation", which will be key to understanding the pathophysiology associated with deficits in rod vision.

描述（由申请人提供）：哺乳动物的视杆视觉非常敏感，在很少有视杆吸收光子的条件下允许视觉。此外，视杆视觉在高于该阈值的光强度中延伸超过8个数量级。本提案中描述的实验旨在阐明基本的视网膜机制，该机制允许视杆光响应与视觉阈值附近的噪声的区分，并允许视杆光响应通过在宽范围的光强度上的几个平行通路被传输到视网膜神经节细胞。为了实现这些目标，我们建议记录野生型和几种转基因小鼠品系的视杆细胞和下游视网膜神经元（双极细胞，无长突细胞和神经节细胞）的光诱发反应。我们的目标是回答几个基本的问题，如何杆光反应的视网膜电路内处理和解析。首先，我们建议确定的限制源的噪声在杆光感受器，设置视觉阈值，利用小鼠模型，减少杆噪声。我们将比较减少的噪声如何影响单光子响应的检测，以及它如何影响行为阈值。视杆细胞中的极限噪声反映了视杆细胞光转导中的一个关键控制点，该控制点设定了绝对视觉阈值。第二，我们提出的主要杆路径中的杆驱动信号的特性，并确定如何在适应背景光的灵敏度调制。最后，我们建议如何锥双极细胞集成杆驱动的信号所产生的主要和次要的杆途径，沿着与锥驱动的信号，使用小鼠，无论是杆或锥光转导已被沉默。这些实验将使我们能够剖析如何杆驱动的信号在许多平行的路径联合收割机与锥驱动的信号，以定义杆视觉的动态范围。我们的长期目标是提供一个全面的了解机制，控制杆驱动的信号传输到更高的视觉中心。这项工作与NEI视网膜疾病计划的目标一致，“使用分子和生理学方法来识别适应的感光后神经成分”，这将是理解与视杆视觉缺陷相关的病理生理学的关键。