Synaptic transmission at retinal ribbon synapses

视网膜带突触的突触传递

• 批准号: 10544542
• 负责人: WALLACE B THORESON
• 金额: $ 46.74万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10544542
• 关键词: Action Potentials; Affect; Afferent Neurons; Amacrine Cells; Animal Model; Animals; Anions; Auditory system; Binding; Biological Assay; Blindness; Calcium; Cells; Charge; Communication; Coupled; Darkness; Data; Disease; Docking; Electric Capacitance; Electrophysiology (science); Electroretinography; Excision; Exhibits; Exocytosis; Eye; Genetic; Glutamate Transporter; Glutamates; Grant; Hair Cells; Hearing; Image; Individual; Inherited; Inner Hair Cells; Investigation; Kinetics; Knockout Mice; Laboratories; Labyrinth; Location; Measures; Membrane; Membrane Potentials; Mental Depression; Mental Health; Modeling; Monitor; Morphology; Movement; Multiprotein Complexes; Mus; Nervous System; Neurons; Neurotransmitters; Organelles; Photoreceptors; Physiological; Physiology; Process; Property; Proteins; Recovery; Retina; Rod; Role; Sensory; Site; Speed; Structure; Synapses; Synaptic Transmission; Synaptic Vesicles; Testing; Transgenic Organisms; Travel; Uncertainty; Vertebrate Photoreceptors; Vesicle; Vision; Visual System; Zebrafish; cell type; deafness; electrical property; experimental study; imaging study; knockout animal; meter; nervous system disorder; neurotransmission; neurotransmitter release; presynaptic; presynaptic neurons; recruit; ribbon synapse; sensory stimulus; transmission process; vesicular release; voltage clamp

In sensory cells of the eye and inner ear the neurotransmitter glutamate is released at active zones in a graded and continuous manner. These cells have evolved specialized structures known as synaptic ribbons. These proteinaceous structures tether synaptic vesicles near active zones. Based on their location, abundance of tethered vesicles, and properties of the sensory neurons in which they are found, these organelles have long been thought to be important for maintaining the continuous release of glutamate. Several other functions have also been ascribed to ribbons. However, recent evidence casts doubt on these ideas. The focus of this grant is to understand the role of synaptic ribbons in sensory synaptic transmission using animal models that lack Ribeye, a protein that is both the most abundant within the ribbon and not found anywhere else. Lack of Ribeye leads to loss of membrane associated synaptic ribbons, without loss of other presynaptic proteins. Specific Aim 1 investigates how Ribeye removal and loss of synaptic ribbons affects neurotransmitter release from photoreceptors. Specific Aim 2 looks at the properties of synaptic release in bipolar cells from the same animals. In Specific Aim 3, we will image single synaptic vesicles in cells lacking Ribeye to measure rates of vesicle movement and replenishment to test the role of the ribbon in these processes. Understanding ribbon function may provide clues to help understand diseases that specifically affect vision and hearing. In addition, the fundamental understanding of presynaptic processes in these specialized neurons will have broader implications for neuronal communication in general and thus, may contribute to our understanding of various aspects of mental health and neurological disorders.

在眼睛和内耳的感觉细胞中，神经递质谷氨酸在活跃区域按等级释放。 并持续的方式。这些细胞已经进化出称为突触带的特殊结构。这些 蛋白质结构将突触小泡束缚在活性区域附近。根据其位置，丰富的 由于栓系囊泡以及它们所在的感觉神经元的特性，这些细胞器长期以来 被认为对于维持谷氨酸的持续释放很重要。其他几个功能有 也被归因于丝带。然而，最近的证据对这些想法提出了质疑。此次资助的重点是 使用缺乏的动物模型来了解突触带在感觉突触传递中的作用 肋眼肉，一种蛋白质，在丝带中含量最丰富，而且在其他任何地方都找不到。缺乏肋眼牛排 导致膜相关突触带的损失，而不损失其他突触前蛋白。具体目标 1 研究了肋眼切除和突触带丢失如何影响神经递质的释放 光感受器。具体目标 2 研究同一动物双极细胞突触释放的特性。 在特定目标 3 中，我们将对缺乏 Ribeye 的细胞中的单个突触囊泡进行成像，以测量囊泡的比率 移动和补充来测试色带在这些过程中的作用。了解功能区功能 可能提供线索来帮助了解特别影响视力和听力的疾病。此外， 对这些特殊神经元突触前过程的基本理解将产生更广泛的影响 一般而言，神经元通讯可能有助于我们理解神经元通讯的各个方面 心理健康和神经系统疾病。