Functional characteristics of rod pathways in the retina

描述(申请人提供)：哺乳动物的杆状视觉非常敏感，可以在极少杆状吸收光子的条件下视觉。此外，杆状视觉在超过这个阈值的光强度上延伸超过8个数量级。这项建议中描述的实验旨在阐明视网膜的基本机制，这些机制允许在视觉阈值附近区分杆状光反应和噪声，并允许杆状光反应在广泛的光强度范围内通过几个平行的路径传递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个转基因小鼠品系的杆状感光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，关于视杆细胞的光反应是如何在视网膜回路中处理和解析的。首先，我们建议通过利用降低了杆状噪声的小鼠模型来识别杆状感光器中设置视觉阈值的限制源。我们将比较降低的噪声如何影响单光子响应的检测，以及它如何影响观看的行为阈值。杆状结构中的限幅噪声反映了杆状结构光传导中的一个关键控制点，它设置了绝对视觉阈值。其次，我们建议表征初级视杆通路中视杆驱动信号的特性，并确定在适应背景光的过程中敏感度是如何被调制的。最后，我们建议利用视杆细胞或视锥细胞光转导已经沉默的小鼠，研究视锥双极细胞如何整合由初级和次级视杆通路产生的视杆驱动信号，以及视锥驱动信号。这些实验将使我们能够剖析许多平行路径中的杆状驱动信号如何与锥体驱动的信号相结合来定义杆状视觉的动态范围。我们的长期目标是全面了解控制杆状驱动信号传输到高级视觉中心的机制。这项工作与NEI视网膜疾病计划的目标一致，即使用分子和生理学方法识别适应的光感受器后神经成分，这将是理解与视杆视觉缺陷相关的病理生理学的关键。

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.