Role of GABAc Receptor Mediated Inhibition in Retinal Visual Function

视网膜是一个分层的结构，每一层都由不同的细胞种类组成。大多数细胞类别根据它们的形状以及它们接收的兴奋性和抑制性输入进一步细分。在视网膜以及大脑的其他部分，抑制通过调节兴奋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。GABA由突触后细胞通过三种受体之一检测：GABAA、GABAB或GABAC。每种GABA受体都可以通过其结构、对GABA的敏感性以及对不同激动剂和拮抗剂的选择性来鉴定。这些受体在大脑中的表达模式也不同。这些结构和功能上的差异导致了一种假设，即每个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性输出，并因此最终调节视网膜的整体视觉响应。拟定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）。检查GABAC缺失小鼠视网膜的解剖结构，并与对照比较，以确定GABAC受体的缺失是否改变视网膜结构。将在GABAC缺失小鼠中评估视网膜中所有细胞的视觉反应，并使用非侵入性技术视网膜电图与对照进行比较。这些数据将确定GABAC介导的抑制的缺乏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使用分子遗传操作来定义视网膜中抑制性输入的功能

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