Synaptic transmission at retinal ribbon synapses

视网膜带突触的突触传递

• 批准号: 10154012
• 负责人: WALLACE B THORESON
• 金额: $ 50.59万
• 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/10154012
• 关键词: Action Potentials; Affect; Afferent Neurons; Amacrine Cells; Animal Model; Animals; Anions; Auditory system; Biological Assay; Blindness; Calcium; Cells; Charge; Communication; Coupled; 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 structure; Neurons; Neurotransmitters; Organelles; Photoreceptors; Physiological; Physiology; Process; Property; Proteins; Recovery; Retina; Rod; Role; Sensory; Signal Transduction; Site; Speed; Structure; Synapses; Synaptic Transmission; Synaptic Vesicles; Testing; Transgenic Organisms; Travel; Uncertainty; Vertebrate Photoreceptors; Vesicle; Vision; Visual system structure; Zebrafish; base; cell type; deafness; electrical property; experimental study; imaging study; knockout animal; nervous system disorder; neurotransmitter release; presynaptic; presynaptic neurons; recruit; ribbon synapse; sensory stimulus; 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按分级释放