Contribution of rod photoresponse inactivation kinetics to visual temporal contrast sensitivity in mesopic light.

视杆细胞光响应失活动力学对中间光中视觉时间对比敏感度的贡献。

• 批准号: 10578821
• 负责人: EDUARDO C SOLESSIO
• 金额: $ 42.14万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10578821
• 关键词: Area; Awareness; Behavior; Behavioral; Behavioral Assay; Biological Assay; Calcium; Collection; Complement; Cone; Contrast Sensitivity; Diagnostic; Disabled Persons; Electrophysiology (science); Environment; Exhibits; Exposure to; Feedback; Frequencies; Funding; Future; Generations; HCN1 channel; HCN1 gene; Kinetics; Knock-out; Knowledge; Light; Lighting; Mediating; Modeling; Molecular; Mus; Night Blindness; Outcome; Pathologic; Patients; Perforation; Persons; Phase; Phototransduction; Physiology; Play; Public Health; Publishing; Research; Retina; Retinal Degeneration; Retinitis Pigmentosa; Rod; Role; Shapes; Signal Transduction; Speed; Stimulus; System; Testing; Therapeutic; Time; Transgenes; Transgenic Mice; Variant; Vertebrate Photoreceptors; Vision; Visual; Visual System; Work; desensitization; experience; genetic manipulation; innovation; mouse genetics; novel; overexpression; quantum; rapid detection; response; retinal rods; seal; visual control; visual processing; voltage; voltage gated channel

Project Summary Rod-mediated vision transitions seamlessly to cone-mediated vision as light levels rise through the mesopic visual range. Despite the fact that mesopic vision is the major mode of vision for people who spend most of their time indoors under artificial lighting, there is a glaring lack of knowledge of how rod and cone photoresponses shape the temporal, spatial, and spectral sensitivities of mesopic vision. For decades it has been accepted that rods subserve vision in dim scenes, detecting only slow variations in light levels (contrast), and cones subserve vision in bright scenes when contrast changes rapidly. Our recently published results show that at indoor (mesopic) light levels, rods drive the visual responses to fast — not slow — temporal variations. Our findings reveal, for the first time, that adaptation of both rod and cone-driven visual responses underlie the seamless transition between scotopic and photopic vision over the mesopic range, but we do not understand how this happens. Therefore, there is a critical need to understand the physiology and functional significance of rod responses at mesopic, indoor light levels. In this application our objectives are: (i) to determine the adaptation mechanisms that control the responses of rods to slow and fast light variations in mesopic lights, and (ii) to determine the behavioral significance of rod-driven visual responses to fast changing scenes in mesopic lights. Our model is that a hierarchical system of adaptation mechanisms is in place to differentially regulate rod sensitivity as lights rise through the mesopic range. To test this model we propose two related but independent aims that investigate the underlying cellular and perceptual mechanisms. These aims are to determine 1) how rods respond to slow and fast variations in mesopic lights, and 2) the behavioral significance of inner segment conductances to the adaptation of rod visual responses in mesopic lights. For the first aim we will combine the power of mouse genetics, electrophysiological recordings, quantitative modeling, and operant behavioral assays to determine how different phototransduction adaptation mechanisms, including background and bleaching adaptation, work together to differentially regulate the responses to slow and fast light variations and to overcome the crippling effects of response compression in mesopic illumination. For the second aim, we will use mice with rod-specific knockout of voltage-gated conductances that are typically activated at mesopic lights to probe the functional significance of inner segment conductances to rod-driven responses in mesopic lights. Our expected outcome is to provide evidence for mechanisms that the visual system uses to encode signal variations in mesopic lights (Advancement of Basic Knowledge). Knowledge of this mechanisms will open new strategies for understanding and treating retinal pathological conditions, with implications beyond this particular application (Innovation for Emerging Therapy).

项目摘要 视杆介导的视觉无缝地过渡到视锥介导的视觉， 中间视觉范围尽管中间视觉是人们的主要视觉模式， 他们大部分时间在室内人工照明下，明显缺乏关于杆和锥如何 光响应形成中间视觉的时间、空间和光谱灵敏度。几十年来， 已经接受的是，杆在昏暗的场景中有助于视觉，仅检测光水平（对比度）的缓慢变化， 并且当对比度快速变化时，锥体在明亮的场景中帮助视觉。我们最近公布的结果显示 在室内（中间视觉）光照水平下，视杆细胞驱动视觉反应快速-而不是缓慢-时间变化。 我们的研究结果首次揭示了视杆细胞和视锥细胞驱动的视觉反应的适应性是 在中间视觉范围内暗视觉和明视觉之间的无缝过渡，但我们不明白 这是怎么发生的因此，迫切需要了解的生理和功能意义， 视杆细胞对室内光线的反应。在本申请中，我们的目标是：（i）确定适应性 控制视杆对中间光中的慢光和快光变化的反应的机制，以及（ii） 确定视杆细胞对中间视觉光中快速变化场景的视觉反应的行为意义。 我们的模型是，一个层次系统的适应机制是到位的差异调节杆 当光线穿过中间视觉范围上升时的灵敏度。为了测试这个模型，我们提出了两个相关但独立的 目的是研究潜在的细胞和感知机制。这些目标是确定1）如何 视杆细胞对中间光的慢变化和快变化的反应; 2）内节的行为意义 传导到中间视觉光中的视杆视觉反应的适应。对于第一个目标，我们将联合收割机 小鼠遗传学、电生理学记录、定量建模和操作性行为测定的能力 以确定不同的光转导适应机制，包括背景和漂白， 适应，共同努力，以差异调节反应，以缓慢和快速的光变化，并克服 中间视觉照明中的响应压缩的严重影响。对于第二个目标，我们将使用小鼠， 视杆特异性敲除电压门控电导，其通常在中间光下被激活以探测 内节电导对中间视觉光中视杆驱动反应的功能意义。我们预期的 结果是为视觉系统用于编码信号变化的机制提供证据， mesopic lights（基础知识的进步）。了解这一机制将开辟新的战略， 了解和治疗视网膜病理条件，其影响超出了这一特定的应用 （Innovation for Emerging Therapy）