Connexins and electrical synapses in the retina

视网膜中的连接蛋白和电突触

• 批准号: 7250131
• 负责人: DAVID L PAUL
• 金额: $ 24.69万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7250131
• 关键词: Connexins; electrical; synapses; retina

DESCRIPTION (provided by applicant): In the retina, gap junctions are established by many cell types and may participate in retinal circuitry in a variety of ways. Gap junctions are composed of connexins, encoded by a >20-member family of highly related genes. Only one of these, connexin36 (Cx36), has been conclusively demonstrated in retinal neurons. Using a Cx36 knockout (KO) mouse incorporating a histochemical reporter, we found Cx36 to be present in most or all All amacrine cells, many photoreceptors, subsets of ON and OFF cone bipolar cells and a low number of ganglion cells. However, horizontal cells and many ganglion cells establish gap junctions yet do not express Cx36. Using RT-PCR, we have found Cx45 and Cx57 to be prominently expressed in mouse retina. We propose to characterize the cellular distribution of these connexins and determine if other gap junction channel-forming proteins may be present in retinal neurons. Many lines of evidence indicate that rod photoreceptor signals utilize multiple pathways to reach ganglion cells. In our Cx36 KO, ON ganglion cell responses to scotopic stimuli are completely eliminated, indicating that Cx36 is required in all pathways contributing to rod ON signaling. We showed that gap junctional coupling between AII and cone ON bipolar cells, the presumed 'primary' pathway for rod photoreceptor signaling, was abolished in the KO. Since a proposed 'alternative' pathway involved gap junction between rods and cones, and since we found Cx36 expression in photoreceptors, our findings were consistent with the proposed 'alternative' pathway. However, recent studies of retinas from mice genetically altered to lack cones suggest that rod-cone coupling does not contribute to rod photoreceptor signaling. In addition, it has not been technically feasible to measure junctional coupling between photoreceptors in mouse retinas. Therefore, to resolve the discrepancy between current models of the 'alternative' pathway, we will 1) develop a method to directly assess rod-cone coupling in WT and Cx36 KO mice and 2) produce conditional knockouts that eliminate Cx36 specifically from either cones or from AII amacrine cells. Then, ganglion cell responses to light can be assessed in retinas where either primary or alternative pathways are ablated.

描述（由申请人提供）：在视网膜中，间隙连接由许多类型的细胞建立，并可能以多种方式参与视网膜回路。间隙连接由连接蛋白组成，由高度相关的20个基因组成的家族编码。其中只有一种，connexin36 (Cx36)，在视网膜神经元中被证实存在。使用含有组织化学报告基因的Cx36敲除（KO）小鼠，我们发现Cx36存在于大多数或所有的all无腺细胞、许多光感受器、ON和OFF锥双极细胞亚群和少量神经节细胞中。然而，水平细胞和许多神经节细胞建立间隙连接却不表达Cx36。利用RT-PCR，我们发现Cx45和Cx57在小鼠视网膜中显著表达。我们建议表征这些连接蛋白的细胞分布，并确定是否其他间隙连接通道形成蛋白可能存在于视网膜神经元中。