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: 8306747
• 负责人: Alapakkam P Sampath
• 金额: $ 41万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8306747
• 关键词: Amacrine Cells; Behavioral; Cells; Characteristics; Dendrites; Detection; Discrimination; Equilibrium; Functional disorder; Gap Junctions; Goals; Inherited; Light; Light Adaptations; Lighting; Mammals; Measures; Molecular; Mouse Strains; Mus; Noise; Output; Pathway interactions; Photons; Photophobia; Photoreceptors; Phototransduction; Physiological; Presynaptic Terminals; Process; Property; Relative (related person); Retina; Retinal; Retinal Cone; Retinal Diseases; Retinal Ganglion Cells; Rhodopsin; Signal Transduction; Source; Synapses; Synaptic Transmission; System; Testing; Transgenic Mice; Vertebrate Photoreceptors; Vision; Visual; Water; Wild Type Mouse; Work; absorption; base; behavior influence; driving force; ganglion cell; improved; insight; light intensity; mouse model; programs; relating to nervous system; research study; response; retinal bipolar neuron; retinal rods; transmission process; visual threshold; voltage; voltage clamp

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也能看到。此外，杆状视觉在光强上超过这个阈值超过8个数量级。本提案中描述的实验旨在阐明视网膜的基本机制，该机制允许视杆光反应从视觉阈值附近的噪声中区分出来，并允许视杆光反应通过几个平行的途径在广泛的光强度范围内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种转基因小鼠品系的杆状光感受器和下游视网膜神经元（双极细胞、无毛细胞和神经节细胞）的光诱发反应。我们的目标是回答几个关于视杆光反应是如何在视网膜回路中处理和解析的基本问题。首先，我们建议利用降低杆噪声的小鼠模型来确定杆状光感受器中设置视觉阈值的限制噪声源。我们将比较降低的噪声如何影响单光子响应的检测，以及它如何影响视觉的行为阈值。杆状体中的限制噪声反映了杆状体光导过程中的一个关键控制点，该控制点设定了绝对视觉阈值。其次，我们建议表征主杆通路中杆驱动信号的特性，并确定灵敏度在适应背景光期间是如何调制的。最后，我们提出表征锥体双极细胞如何整合由主要和次要杆状通路产生的杆状驱动信号，以及锥体驱动信号，使用杆状或锥体光导被沉默的小鼠。这些实验将允许我们剖析杆驱动信号在许多平行路径中如何与锥驱动信号相结合，以定义杆视觉的动态范围。我们的长期目标是全面了解控制杆状驱动信号向高级视觉中心传输的机制。这项工作与NEI视网膜疾病项目的目标是一致的，“使用分子和生理方法来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。