Voltage-gated calcium channels in the development of photoreceptor synapses

项目摘要/摘要 这项提案的总体目标是为申请者提供成为 视觉研究领域的独立调查者。研究计划的目标是确定 调节视网膜中突触的信息传输的过程，以使光线 关于后天和遗传性视力丧失的治疗策略。在视网膜中，光感受器 将光模式中的变化作为神经信号在称为 “带状”突触。这些突触的发育和成熟功能的变化导致视力 对人类的损害。这种信息的传输由电压门控的Cav1钙通道来协调。 本研究的目的是建立电压门控性钙通道在心肌细胞内的作用。 应用最新技术发展和维持光感受器带突触 显微镜(共焦、超分辨率、连续块面扫描电子显微镜)和贴片 钳夹电生理学结合对Cav1通道表达改变的小鼠的分析。 目标1将定义Cav1.4通道在杆状突触和锥体突触初始组装中的作用，而 目标2将确定Cav1.3通道在维持锥体突触方面的具体作用。 该研究计划将提供发育神经生物学、哺乳动物视网膜 电生理学，最先进的显微镜和成像，实验设计和严谨，以及 对复杂数据集的定量分析。培训活动包括机构支助的活动 改善教师精神、科学写作、口头交流和指导。

PROJECT SUMMARY/ABSTRACT The overall objective of this proposal is to provide the applicant with training needed to become an independent investigator in the field of vision research. The goal of the research plan is to define processes that regulate the transmission of information at synapses in the retina, in order to shed light on therapeutic strategies for acquired and inherited forms of vision loss. In the retina, photoreceptors communicate the changes in light patterns as a neural signal at specialized connections known as “ribbon” synapses. Alterations in the development and mature function of these synapses cause vision impairment in humans. This transfer of information is coordinated by voltage-gated Cav1 Ca2+ channels. The objective of this proposal is to establish the roles of voltage-gated Cav1 Ca2+ channels in the development and maintenance of photoreceptor ribbon synapses using state-of the art techniques in microscopy (confocal, super-resolution, serial block face scanning electron microscopy) and patch clamp electrophysiology in combination with analyses of mice with altered expression of Cav1 channels. Aim 1 will define the role of the Cav1.4 channel in the initial assembly of rod and cone synapses while Aim 2 will determine the role of the Cav1.3 channel for the maintenance specifically of cone synapses. The research plan will provide training in developmental neurobiology, mammalian retinal electrophysiology, state-of the art microscopy and imaging, experimental design and rigor, and quantitative analyses of complex datasets. Training activities include institutionally supported activities to improve grantsmanship, scientific writing, oral communication, and mentorship.