Light Adaptation and Circadian Modulation

光适应和昼夜节律调节

• 批准号: 9090123
• 负责人: Gregory Darin Field
• 金额: $ 39.75万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9090123
• 关键词: Area; Biological Assay; Brain; Cell physiology; Circadian Rhythms; Cone; Coupling; Data; Development; Dopamine; Electrophysiology (science); Environment; Exhibits; Gap Junctions; Goals; Health; Knowledge; Light; Light Adaptations; Lighting; Measures; Mediating; Melatonin; Morphology; Mus; Nature; Neural Retina; Outcome; Output; Paracrine Communication; Pathway interactions; Phase; Photoreceptors; Population; Process; Property; Public Health; Pupil light reflex; Research; Retina; Retinal; Retinal Degeneration; Retinal Diseases; Retinal Ganglion Cells; Signal Transduction; Signaling Molecule; Stem cells; System; Techniques; Technology; Testing; Vertebrate Photoreceptors; Vision; Visual; Work; cell type; coping; extrastriate visual cortex; gene therapy; innovation; multi-electrode arrays; parallel processing; photoreceptor disc; programs; receptive field; relating to nervous system; response; retinal prosthesis; retinal rods; signal processing; visual information; visual process; visual processing; visual stimulus

DESCRIPTION (provided by applicant): There is a fundamental gap in understanding how the parallel processing of visual information performed by the retina is modified by light adaptation and the circadian cycle. The existence of this gap precludes an understanding of how visual scenes are encoded by the retina, and decoded by the brain, across the diverse visual environments encountered from night to day. The objective here is to identify how light adaptation with the circadian cycle alters retinal ganglion cell (RGC) function. RGCs consist of ~20 distinct types. Each type carries different information about the visual scene to the brain. Cumulatively, the RGCs send this information to ~25 different brain areas. To cope with the diverse lighting conditions of natural environments, light adaptation and the circadian cycle dovetail to dynamically modulate retinal function. Dopamine and melatonin are two key signaling molecules in this process. Yet, their net impact on modulating visual signals across diverse RGC types remains elusive. The central hypothesis is that light adaptation, bolstered by the circadian cycle, exerts different changes in different RGC types. To test this hypothesis, this proposal has three specific aims: (1) determine the impact of light adaptation on response properties in many RGC types; (2) determine the impact of circadian cycle on response properties in many RGC types; and (3) determine the impact of two key circadian signals, dopamine and melatonin, on RGC function. Electrophysiological recording will be made from hundreds of RGCs simultaneously using a large-scale multielectrode array. Diverse visual stimuli will be presented to the isolated retina while recording from the RGCs to determine their light response properties. These response properties will be measured at different light levels and during different phases of the circadian cycle. Mouse lines with disrupted dopamine and/or melatonin signaling, will be used to understand how these molecules alter RGC responses under diverse lighting conditions. The proposed research is innovative because it utilizes a recently developed large-scale parallel neural recording technology to determine the interplay between parallel processing, light adaptation and the circadian cycle. The proposed research is significant because it will provide major advances in our understanding of how neural populations in the retina adapt to changes in light level, and how this adaptation is modulated by the circadian cycle. Further, these data will provide strong constraints in three areas: (1) how cellular and circuit mechanisms in the retina contribute to light adaptation and circadian modulation of visual signaling; (2) how central visual areas process retinal signals across light levels between night and day; and (3) the development of computational and theoretical principles for describing and explaining the functional impact of light adaptation. Ultimately this research will unify our understanding of the two most central functions of the neural retina: establishing the parallel processing of visual information and adapting to diverse visual environments.

描述（由申请人提供）：在理解视网膜执行的视觉信息的并行处理如何通过光适应和昼夜节律周期进行修改方面存在根本性的差距。这种间隙的存在阻碍了我们对视觉场景如何在从夜间到白天遇到的不同视觉环境中由视网膜编码和由大脑解码的理解。这里的目标是确定昼夜节律周期的光适应如何改变视网膜神经节细胞（RGC）的功能。 RGC 由约 20 种不同的类型组成。每种类型都向大脑传递有关视觉场景的不同信息。 RGC 累计将这些信息发送到约 25 个不同的大脑区域。为了应对自然环境的多样化光照条件，光适应与昼夜节律周期相吻合，动态调节视网膜功能。多巴胺和褪黑激素是这个过程中的两个关键信号分子。然而，它们对调节不同 RGC 类型的视觉信号的净影响仍然难以捉摸。核心假设是，昼夜节律周期支持的光适应在不同的 RGC 类型中产生不同的变化。为了检验这一假设，该提案具有三个具体目标：（1）确定光适应对许多 RGC 类型的响应特性的影响； (2) 确定昼夜节律周期对多种 RGC 类型的反应特性的影响； (3) 确定两个关键的昼夜节律信号：多巴胺和褪黑激素对 RGC 功能的影响。将使用大规模多电极阵列同时对数百个 RGC 进行电生理记录。不同的视觉刺激将呈现给孤立的视网膜，同时从 RGC 进行记录以确定其光响应特性。这些响应特性将在不同的光照水平和昼夜节律周期的不同阶段进行测量。多巴胺和/或褪黑激素信号传导被破坏的小鼠品系将用于了解这些分子如何在不同的光照条件下改变 RGC 反应。这项研究具有创新性，因为它利用了最近开发的大规模并行神经记录技术来确定并行处理、光适应和昼夜节律周期之间的相互作用。这项研究意义重大，因为它将为我们理解视网膜中的神经群体如何适应光照水平的变化，以及这种适应如何受到昼夜节律周期的调节提供重大进展。此外，这些数据将在三个领域提供强有力的约束：（1）视网膜中的细胞和电路机制如何促进视觉信号的光适应和昼夜节律调节； （2）中央视觉区域如何处理夜间和白天不同光照水平下的视网膜信号； （3）用于描述和解释光适应的功能影响的计算和理论原理的发展。最终这个 研究将统一我们对神经视网膜两个最核心功能的理解：建立视觉信息的并行处理和适应不同的视觉环境。