Development of Specializations Required for Temporal Coding in Octopus Cells

章鱼细胞时间编码所需专业化的发展

• 批准号: 10541129
• 负责人: Lauren J Kreeger
• 金额: $ 7.17万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10541129
• 关键词: Acoustic Nerve; Acoustics; Action Potentials; Acute; Adult; Anatomy; Animals; Auditory; Auditory Brain Stem Implants; Auditory system; Awareness; Binding; Biological Models; Biophysics; Brain; Brain Stem; Cell Extracts; Cell physiology; Cells; Characteristics; Child; Cochlea; Cochlear Implants; Cochlear nucleus; Code; Communication; Comprehension; Continuing Education; Cues; Data; Dendrites; Detection; Development; Distal; Ear; Electrophysiology (science); Environment; Fire - disasters; Frequencies; Glean; Goals; Hearing; Image Analysis; Ion Channel; Ion Channel Gating; Leadership; Mammalian Cell; Maps; Measures; Mentorship; Methods; Modeling; Molecular Analysis; Molecular Genetics; Morphology; Mus; Nervous system structure; Neurobiology; Neurons; Octopus; Pathway interactions; Patients; Pattern; Perception; Phase; Physiological; Play; Population; Preparation; Property; Reporting; Research; Research Training; Role; Sensory; Slice; Speech; Speech Perception; Stimulus; Synapses; System; Time; Training; auditory pathway; biophysical analysis; biophysical properties; career; developmental neurobiology; experience; experimental study; feature extraction; improved; insight; medical schools; nerve supply; neuron development; neuronal cell body; neuronal circuitry; normal hearing; parallel processing; sensory mechanism; sensory system; skills; sound; voltage

Project Summary The auditory system is an ideal place to study how neurons and circuits develop to encode sensory features with temporal precision. In the cochlear nucleus, specialized cells extract information about the acoustic world and initiate parallel processing pathways, each of which analyzes and encodes continuous auditory cues such as frequency, phase, and amplitude. The octopus cell of the mammalian cochlear nucleus stands out for its unique sensitivity to both the temporal and frequency components of sound stimuli. However, the mechanisms underlying development of tonotopically organized somatic and dendritic synapses in single neurons is not understood. Additionally, there is little understanding of the role of auditory experience in the refinement of morphological and physiological properties that contribute to temporal coding. I propose to carry out an integrated analysis of the molecular and biophysical properties of octopus cells and to track how features develop during the onset of auditory experience. Using the mouse as a model system, I will define the refinement of tonotopically organized inputs to octopus cell somas and dendrites before and after hearing onset while parallel changes in the size and complexity of the dendritic arbor occur. This data will provide insights into the role of auditory experience on the development of brainstem auditory circuits. I will also measure correlated changes in ion channel expression with changes in biophysical properties at developmental timepoints and measure electrophysiological changes as auditory experience first begins. These experiments will bridge the sequence of anatomical refinements with physiological refinements during hearing onset. The research training plan will provide extensive training in developmental neurobiology, methods in mouse molecular genetics, quantitative approaches, and computational image analysis. Training will occur in the rich scientific environment at Harvard Medical School in the Department of Neurobiology. Additionally, the training plan includes continuing education in mentorship, communication, management, diversity, and leadership. The training provided under this plan will provide essential skills for a successful independent research career.

项目摘要 听觉系统是研究神经元和电路如何开发以与感官特征一起使用的理想场所 时间精度。在人工耳蜗中，专门的细胞提取有关声学世界和的信息 启动并行处理途径，每种途径分析和编码连续的听觉线索，例如 频率，相和振幅。哺乳动物人工耳蜗核的章鱼细胞以其独特而脱颖而出 对声刺激的时间和频率成分的敏感性。但是，机制 单个神经元中的体点组织的体细胞和树突突触的潜在发展不是 理解。此外，对听觉经验在完善中的作用几乎没有理解 有助于时间编码的形态和生理特性。 我建议对章鱼细胞的分子和生物物理特性进行综合分析以及 跟踪在听觉体验开始期间的功能如何发展。使用鼠标作为模型系统，我将 定义对章鱼细胞躯体和树突的调整的细化，以前和之后 听力发作同时发生了树突状乔木的大小和复杂性的平行变化。这些数据将提供 洞悉听觉经验在脑干听觉电路发展中的作用。我也会衡量 离子通道表达的相关变化与发育时点生物物理特性的变化 并在听觉经验首次开始时测量电生理变化。这些实验将桥接 在听力发作过程中，解剖学改进与生理改进的顺序。 研究培训计划将提供广泛的发育神经生物学，鼠标方法的培训 分子遗传学，定量方法和计算图像分析。培训将在富人中进行 神经生物学系哈佛医学院的科学环境。此外，培训 计划包括继续教育指导，沟通，管理，多样性和领导力。这 根据本计划提供的培训将为成功的独立研究职业提供基本技能。