Role of GABAc Receptor Mediated Inhibition in Retinal Visual Function

视网膜是一个分层结构，每一层都由不同的细胞类填充。大多数细胞类别根据它们的形状和它们接受的兴奋性和抑制性输入进一步细分。在视网膜和大脑的其他部位，抑制作用通过调节兴奋性信号在神经元功能中起着核心作用。大多数抑制性神经传递是由突触前细胞释放甘氨酸或γ氨基丁酸（GABA）介导的。突触后细胞通过三种受体之一检测GABA: GABAA、GABAB或GABAC。每种GABA受体可以通过其结构、对GABA的敏感性和对不同激动剂和拮抗剂的选择性来识别。这些受体在大脑中的表达方式也不同。这些结构和功能上的差异导致了一种假设，即每种GABA受体在神经系统中介导不同类型的抑制。在啮齿动物视网膜中，GABAC受体仅位于双极细胞的轴突末端。因此，GABAC受体应该能够调节双极细胞的兴奋输出，从而最终调节视网膜的整体视觉反应。提出的实验将使用通过分子遗传操作消除GABAC受体的小鼠（GABAC无效小鼠）。研究人员将检查GABAC缺失小鼠视网膜的解剖结构，并与对照组进行比较，以确定GABAC受体的缺失是否会改变视网膜结构。在GABAC无效的小鼠中，所有视网膜细胞的视觉反应将被评估，并使用一种非侵入性技术——视网膜电图与对照组进行比较。这些数据将确定GABAC介导的抑制缺失如何影响视网膜水平的视觉反应。这些实验代表了首次尝试定义视网膜中抑制性输入的功能，使用分子遗传操作

The retina is a layered structure and each layer is populated by different cell classes. Most cell classes are further subdivided on the basis of their shape and on the excitatory and inhibitory inputs they receive. In the retina, as well as in the rest of the brain, inhibition plays a central role in neuronal function by modulating excitatory signals. Most inhibitory neurotransmission is mediated by the release of either glycine or gamma amino butyric acid (GABA) from the pre-synaptic cell. GABA is detected by the post-synaptic cell by one of three receptors: GABAA, GABAB or GABAC. Each GABA receptor can be identified by its structure, sensitivity to GABA and selectivity for different agonists and antagonists. These receptors also differ in their pattern of expression in the brain. These structural and functional differences lead to the hypothesis that each GABA receptor mediates a different type of inhibition in the nervous system. In the rodent retina, the GABAC receptor is located only on the axon terminals of bipolar cells. Thus, the GABAC receptor should be able to modulate the excitatory output of the bipolar cells and, thus, ultimately modulate to the overall visual response of the retina. The proposed experiments will use a mouse in which the GABAC receptor was eliminated (GABAC null mouse) via molecular genetic manipulations. The anatomy of the retina of the GABAC null mice will be examined and compared to controls to determine if the absence of the GABAC receptor alters retinal structure. The visual responses of all of the cells in the retina will be assessed in the GABAC null mice and compared to controls using a non-invasive technique, the electroretinogram. These data will determine how the absence of GABAC mediated inhibition affects the visual response at the level of the retina. These experiments represent the first attempt to define the function of an inhibitory input in the retina, using molecular genetic manipulations