Cellular Mechanisms of High-Acuity Vision

 描述(申请人提供)：人类大多数有意识的视觉依赖于中心凹，这是一种视网膜结构，对图像进行了极其详细的编码。我们的目标是了解中心凹信号编码的第一步，这发生在它不同寻常的光感受器群体中。这些中心凹视锥在形态上与外围视网膜中的对应视锥不同。中心凹视锥具有微小的横截面和致密的堆积，这使得它们可以形成独特的精细像素阵列。它们还将长轴突延伸到突触后细胞。这使得视网膜回路可以从中心凹视锥的光路横向移位，从而使视觉图像变得清晰。我们的假设是，除了这些解剖特征外，中心凹视锥还有支持图像细节分辨率的生理特化。有理由认为它们的生理功能确实与外周锥体不同。为 例如，它们不寻常的形状可能会影响光传导的生化反应以及从光传导部位到突触终末的信号传播的性质。我们建议定义中心凹视锥细胞光传导的生物物理机制(目标1)，并确定这些细胞的被动和主动膜特性如何进一步塑造沿着轴突向下扩散的光反应(目标2)。我们的方法集中在体外膜片钳电生理学，应用于完整视网膜内的视锥细胞或通过酶解离分离。我们已经建立了一个物流和技术框架，为我们提供中心凹组织，并允许我们从这些脆弱的细胞中进行记录。我们提出的实验是在细胞神经生理学水平上全面了解中心凹的早期步骤。

 DESCRIPTION (provided by applicant): Most conscious vision in humans relies upon the fovea, a retinal structure that encodes the image in exceptional detail. Our goal is to understand the first steps of signal encoding in the fovea, which take place within its unusual population of photoreceptors. These foveal cones are morphologically distinct from their counterparts in the peripheral retina. Foveal cones have a tiny cross-section and dense packing, which allows them to form a uniquely fine pixel array. They also extend long axons to their postsynaptic cells. This allows the retinal circuitry to be displaced laterally from the light path of foveal cones, which sharpens the visual image. Our hypothesis is that, in addition to these anatomical features, foveal cones have physiological specializations that support the resolution of image detail. There is cause to think that their physiology does indeed differ from that of peripheral cones. For example, their unusual shape may influence the biochemical reactions of phototransduction as well as the nature of signal propagation from the site of phototransduction to the synaptic terminal. We propose to define the biophysical mechanisms of phototransduction in foveal cones (Aim 1) and to determine how the passive and active membrane properties of these cells further shape the light response as it spreads down the axon (Aim 2). Our approach centers on in vitro patch-clamp electrophysiology, applied to cones within the intact retina or isolated by enzymatic dissociation. We have established a logistical and technological framework that supplies us with foveal tissue and allows us to record from these delicate cells. Our proposed experiments constitute early steps toward a comprehensive understanding of the fovea at the level of cellular neurophysiology.