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，神经递质谷氨酸被释放在分级的活性区 和连续的方式。这些细胞已经进化出了被称为突触色带的专业结构。这些 蛋白质结构在活性区域附近绑扎突触囊泡。根据他们的位置，丰富 绑扎囊泡以及发现它们的感觉神经元的特性，这些细胞器具有很长的 被认为对于维持谷氨酸的连续释放很重要。其他几个功能具有 还归因于丝带。但是，最近的证据对这些想法产生了怀疑。这笔赠款的重点是 了解突触丝带在使用缺乏动物模型的感觉突触传播中的作用 Ribeye，一种蛋白质，在色带中最丰富，在其他任何地方都找不到。缺乏肋眼 导致膜相关的突触缎带的丧失，而不会损失其他突触前蛋白。具体目标1 调查肋眼去除和突触丝的丧失如何影响神经递质从 感受器。特定的目标2探讨了来自同一动物的双极细胞中突触释放的特性。 在特定的目标3中，我们将在缺乏肋眼的细胞中成像单个突触囊泡以测量囊泡的速率 运动和补充以测试色带在这些过程中的作用。了解色带功能 可能会提供线索来帮助理解特别影响视力和听力的疾病。另外， 对这些专业神经元中突触前过程的基本理解将具有更广泛的含义 对于整个神经元的沟通，因此，可能有助于我们对 心理健康和神经系统疾病。