MECHANISMS OF TEMPORAL ENCODING IN RETINAL BIPOLAR CELLS

描述(申请人提供)：我们的视觉系统感知世界是时间、空间和颜色的函数。定义从快速移动到静止的对象的速度的时间(时间)信息被编码在视觉系统中的时间处理路径中。根据神经反应，这些通路大致可分为暂时性通路和持续性通路。前者编码快速变化的视觉信息，而后者编码静态信息。早期的工作表明，这些不同的时间处理路径发生在视网膜神经节细胞中。两个形态不同的神经节细胞(α-和β-神经节细胞)是这两条不同功能通路的起源。最近的研究表明，位于神经节细胞上游的视网膜双极细胞对视觉信息的并行处理至关重要。形态学研究揭示了哺乳动物视网膜中有10多种双极细胞亚型，它们可能启动了编码不同时间信号特征的不同途径。到目前为止，还没有研究涉及哺乳动物视网膜中的每一种双极细胞亚型如何编码时间视觉信息。为了应对这一研究空白，我的目标是了解ON双极细胞每一亚型的时间编码的细胞和分子机制。在这项拟议的研究中，我将研究哺乳动物视网膜中ON双极细胞的每一种亚型如何编码不同的时间视觉信息。首先，我将研究ON双极细胞每个亚型的时间编码的生理学方面(目标1)。接下来，我将研究时间编码的可能分子机制：mGluR6信号引起的细胞内钙增加(目标2)，以及电压门控通道(目标3)。人们越来越难忽视对功能性视网膜假体和分子遗传学方法恢复患病眼睛视力的需求。这项研究将提高我们对视网膜网络中并行处理的理解，这将有助于未来设计功能性视网膜假体和恢复视力的基因疗法。

DESCRIPTION (provided by applicant): Our visual system perceives the world as functions of time, space, and color. The time (temporal) information, defining the speed of an object ranging from fast moving to stationary, is encoded in temporal processing pathways in the visual system. These pathways are broadly classified into transient pathways and sustained pathways based on their neural responses. The former encodes fast changing visual information, whereas the latter encodes static information. Earlier work suggested that these different temporal processing pathways occurred in retinal ganglion cells. Two morphologically different ganglion cells (a- and ¿-ganglion cells) were the origin for these two distinct functional pathways. Recent studies have suggested that retinal bipolar cells, which are upstream of ganglion cells, are critical for the parallel processing of visual information. Morphological studies have revealed more than 10 subtypes of bipolar cells in the mammalian retina, which might initiate distinct pathways encoding different features of temporal signals. To date, no studies have addressed how each subtype of bipolar cell in the mammalian retina encodes temporal visual information. In response to this research gap, my goal is to understand the cellular and molecular mechanisms of temporal encoding in each subtype of ON bipolar cell. In the proposed study, I will investigate how each subtype of ON bipolar cell encodes distinct temporal visual information in the mammalian retina. First, I will examine physiological aspects of temporal encoding in each subtype of ON bipolar cell (Aim 1). Next, I will examine the possible molecular mechanisms of temporal encoding: intracellular Ca++ increase evoked by mGluR6 signaling (Aim 2), and voltage-gated channels (Aim 3). It has become increasingly difficult to ignore the need for a functional retinal prosthesis and molecular genetics approaches to restore vision for diseased eyes. The proposed study will improve our understanding of parallel processing in the retinal network, which will contribute to the future design of a functional retinal prosthesis and sight restoring gene therapies.