Cellular Mechanisms of High-Acuity Vision

 描述（由申请人提供）：人类大多数有意识的视觉依赖于中央凹，这是一种以异常细节编码图像的视网膜结构。我们的目标是了解中央凹中信号编码的第一步，这发生在其不寻常的光感受器群体中。这些中央凹视锥在形态上与周边视网膜中的对应物不同。中央凹锥体具有微小的横截面和密集的堆积，这使得它们能够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。这使得视网膜回路从中央凹锥体的光路横向移位，这使视觉图像变清晰。我们的假设是，除了这些解剖学特征，中央凹视锥具有支持图像细节分辨率的生理特化。我们有理由认为，它们的生理机能确实与周边视锥细胞不同。为 例如，它们不寻常的形状可能影响光转导的生化反应以及从光转导位点到突触末端的信号传播的性质。我们建议定义光转导的生物物理机制，在中央凹视锥（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光响应，因为它向下传播的轴突（目标2）。我们的方法集中在体外膜片钳电生理学，适用于完整的视网膜内的锥或分离的酶解离。我们已经建立了一个后勤和技术框架，为我们提供了中央凹组织，并允许我们从这些微妙的细胞中记录。我们提出的实验构成了在细胞神经生理学水平上全面理解中央凹的早期步骤。

 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.