Synaptic transmission & its modulation in the retina

描述(申请人提供)：抑制是视网膜信息处理的基本要素。外层和内层的侧向抑制通路分别调节光感受器和双极细胞以及双极细胞和神经节细胞之间的视觉信息流。在哺乳动物的视网膜中，这两条侧向通路的确切作用还不是很清楚。GABA(γ-氨基丁酸)是视网膜和中枢神经系统其他部分抑制的重要介质。视网膜的独特之处在于，两类离子型GABA受体GABAA和GABAc介导抑制信号。这些受体已被证明在视网膜中具有不同的功能特性和细胞分布。GABAc受体主要存在于视网膜中，介导更持久的反应，并且比GABAA受体对GABA更敏感。GABAA受体存在于所有视网膜神经元上，而GABAc受体主要位于双极细胞轴突终末，少量位于外丛状层(OPL)。这项拟议工作的目标是确定这两类GABA受体如何参与哺乳动物视网膜视觉信号的形成。GABA受体在哺乳动物视网膜中的确切功能尚不清楚。在内丛状层，GABA是调节视觉信息处理的空间和时间方面的基本信号。然而，目前尚不清楚这些抑制信号是如何被功能不同的GABAA和GABAc受体解析出来的。利用一种缺乏GABAc受体的动物，GABArho1缺失的小鼠，我们将确定GABAA和GABAc受体在内外丛层信号处理中的作用。这项拟议的研究包括两个目标。AIM1将确定GABAA和GABAc受体如何调节双极细胞的反应，双极细胞是第一个将视觉信号划分为不同通道的细胞。目标2将确定这两类GABA受体如何在内丛状层引起空间和时间处理的多样性。这一目标还将评估内外侧抑制在形成神经节细胞反应(视网膜的输出信号)方面的相对作用。

DESCRIPTION (provided by applicant): Inhibition is an essential element in retinal information processing. Lateral, inhibitory pathways in the outer and inner plexiform layers modulate the flow of visual information between photoreceptors and bipolar cells, and bipolar cells and ganglion cells, respectively. In mammalian retina, the precise roles of the two lateral pathways are not well understood. GABA (gamma-aminobutyric acid) is an important mediator of inhibition in the retina, and other parts of the CNS. The retina is unique in that two classes of ionotropic GABA receptors, GABAa and GABAc mediate inhibitory signals. These receptors have been shown to have distinct functional properties and cellular distributions in the retina. GABAc receptors, which are found mainly in the retina, mediate longer lasting responses and are more sensitive to GABA than GABAa receptors. GABAa receptors are found on all retinal neurons, whereas GABAc receptors are located mainly on bipolar cell axon terminals and, to a less extent, in the outer plexiform layer (OPL). The goal of the proposed work is to determine how these two classes of GABA receptors participate in the shaping of the visual signal in the mammalian retina. The precise functional roles of GABA receptors in the mammalian retina are unknown. At the inner plexiform layer, GABA is an essential signal for modulating the spatial and temporal aspects of visual information processing. However, it is not known how these inhibitory signals are parsed out by functionally different GABAa and GABAc receptors. Using an animal that lacks GABAc receptors, the GABArho1 null mouse, we will determine the roles of GABAa and GABAc receptors in signal processing in the inner and outer plexiform layers. The proposed research consists of two aims. Aim1 will determine how GABAa and GABAc receptors modulate responses in bipolar cells, which are the first cells that divide the visual signal into distinct channels. Aim 2 will determine how the two classes of GABA receptors give rise to the diversity of spatial and temporal processing at the inner plexiform layer. This aim will also evaluate the relative roles of inner and outer lateral inhibition in shaping ganglion cell responses, the output signals of the retina.