Light adaptation and circadian modulation of parallel processing in retina

描述(申请人提供)：在理解视网膜对视觉信息的并行处理如何被光适应和昼夜周期改变方面存在着根本的差距。这种差距的存在使我们无法理解视觉场景是如何被视网膜编码的，以及如何由大脑在白天和夜间遇到的不同视觉环境中进行解码的。这里的目的是确定光适应与昼夜节律如何改变视网膜神经节细胞(RGC)的功能。RGC由大约20种不同的类型组成。每种类型将关于视觉场景的不同信息传递到大脑。累积起来，RGC将这些信息发送到大约25个不同的大脑区域。为了应对自然环境中不同的光照条件，光适应与昼夜周期相吻合，动态调节视网膜功能。多巴胺和褪黑素是这一过程中的两个关键信号分子。然而，它们对调制不同类型RGC的视觉信号的净影响仍然难以捉摸。中心假设是在昼夜节律的支持下，光适应在不同类型的RGC中施加不同的变化。为了验证这一假说，这个建议有三个具体的目的：(1)确定光适应对许多类型RGC反应特性的影响；(2)确定昼夜周期对许多RGC类型反应特性的影响；(3)确定两个关键的昼夜信号--多巴胺和褪黑素--对RGC功能的影响。电生理记录将由数百个RGC同时使用大规模多电极阵列进行。当从RGC记录时，不同的视觉刺激将呈现给分离的视网膜，以确定它们的光响应特性。这些响应特性将在不同的光照水平和昼夜周期的不同阶段进行测量。多巴胺和/或褪黑素信号被破坏的小鼠品系，将被用来了解这些分子如何在不同的光照条件下改变RGC反应。这项拟议的研究具有创新性，因为它利用最近发展的大规模并行神经记录技术来确定并行处理、光适应和昼夜周期之间的相互作用。这项拟议的研究具有重要意义，因为它将为我们理解视网膜中的神经细胞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有助于光适应和视觉信号的昼夜调节；(2)中央视觉区域如何处理夜间和白天之间的光水平上的视网膜信号；以及(3)描述和解释光适应的功能影响的计算和理论原理的发展。最终这就是 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。

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.