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动区以分级的方式释放 和连续不断的态度。这些细胞进化出了称为突触带的特殊结构。这些 蛋白结构系住活动区附近的突触小泡。根据他们的位置，丰富的 系留的小泡，以及发现它们的感觉神经元的特性，这些细胞器有很长的 一直被认为是维持谷氨酸持续释放的重要因素。其他几个函数具有 也被归因于丝带。然而，最近的证据让人对这些想法产生了怀疑。这笔赠款的重点是 使用缺乏突触的动物模型来了解突触带在感觉突触传递中的作用 Ribeye，一种在丝带中含量最丰富的蛋白质，在其他地方找不到。缺少Ribeye 导致膜相关突触带的丢失，而不损失其他突触前蛋白。具体目标1 研究核眼的去除和突触带的丢失如何影响神经递质的释放。 光感受器。特定目标2着眼于同一动物双极细胞中突触释放的特性。 在特定的目标3中，我们将成像缺少Ribeye的细胞中的单个突触小泡来测量小泡的速率 移动和补给，以测试丝带在这些过程中的作用。了解功能区功能 可能会提供线索，帮助理解专门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了解将具有更广泛的意义 从而有助于我们理解神经的各个方面。 精神健康和神经紊乱。