Mapping the Connectivity of Cochlear Nucleus Bushy Cells

绘制耳蜗核浓密细胞的连接性

• 批准号: 8145176
• 负责人: Luke Campagnola
• 金额: $ 3.17万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8145176
• 关键词: Acoustic Nerve; Address; Auditory; Auditory system; Brain; Brain Stem; Cell Cycle Kinetics; Cell Nucleus; Cells; Cochlear Implants; Cochlear implant procedure; Cochlear nucleus; Computer Simulation; Conflict (Psychology); Data; Development; Frequencies; Glutamates; Golgi Apparatus; Hearing Aids; Individual; Kinetics; Knowledge; Literature; Location; Maps; Masks; Measures; Membrane; Methods; Midbrain structure; Modeling; Neurons; Noise; Pattern; Presynaptic Terminals; Process; Property; Psychophysiology; Regulation; Relative (related person); Reporting; Research; Role; Signal Transduction; Simulate; Slice; Source; Stereotyping; Structure; Synapses; System; Taxonomy; Testing; Tinnitus; Work; auditory nuclei; base; cell type; computational network modeling; dorsal cochlear nucleus; improved; information processing; insight; interest; network models; postsynaptic; presynaptic; public health relevance; research study; response; sound; stellate cell; theories

DESCRIPTION (provided by applicant): There is a growing appreciation that developing improved cochlear implants and treatments for tinnitus depends on understanding how information is processed in the central auditory nuclei. The cochlear nucleus receives direct input from the auditory nerve, and is one of the most thoroughly studied nuclei in the brain. Its cell types are distinct and its connections are highly stereotyped. Surprisingly, knowledge about synaptic connectivity within the nucleus is rather limited, which has impeded progress in understanding its role in information processing. This proposal examines the function and organization of local circuitry in the anteroventral cochlear nucleus (AVCN). Recent literature describes many different and often conflicting theories about circuit function in the AVCN. In the first aim of this proposal, the connectivity and synaptic kinetics of cells in the AVCN will be examined using focal glutamate uncaging in cochlear nucleus slices. These experiments will reveal basic details about the structure of the AVCN circuit that have previously eluded examination. Of particular interest are the connections from dorsal cochlear nucleus tuberculoventral neurons and local D-stellate neurons. To investigate the functional significance of AVCN circuitry, a computational model of the network will be built based on accurate representations of synaptic kinetics, neuronal membrane properties, and connectivity patterns. This model will be used to compare the abilities of tuberculoventral and D-stellate neurons in basic psychophysical paradigms. Currently no cochlear nucleus network models use biologically determined synaptic kinetics and connectivity. We aim to provide a model that is as physiologically accurate as possible, allowing greater insight into tinnitus, cochlear implantation, and auditory processing. PUBLIC HEALTH RELEVANCE: Our understanding of the auditory system has driven the development of hearing aids and cochlear implants. Progress is currently limited by our poor understanding of the processing that takes place in the auditory brainstem. This research will determine the structure of auditory brainstem circuits and use this information to investigate auditory information processing.

描述（由申请人提供）：越来越多的欣赏是，开发改进的耳蜗植入物和耳鸣的处理取决于理解中央听觉核中信息的处理方式。耳蜗核从听觉神经接收直接输入，是大脑中最彻底研究的核之一。它的细胞类型是不同的，其连接是高度定型的。令人惊讶的是，对核内突触连通性的知识相当有限，这在理解其在信息处理中的作用方面阻碍了进步。该提案研究了前腹人工耳蜗（AVCN）中局部电路的功能和组织。最近的文献描述了关于AVCN中电路功能的许多不同且通常是冲突的理论。 在该提案的第一个目的中，将使用耳蜗核切片中的局灶性谷氨酸未药物检查AVCN中细胞中细胞的连通性和突触动力学。这些实验将揭示有关先前已经避免检查的AVCN电路结构的基本细节。特别令人感兴趣的是背侧耳蜗核结核核元和局部D型神经元的连接。 为了研究AVCN电路的功能意义，将基于突触动力学，神经元膜特性和连接模式的准确表示网络的计算模型。该模型将用于比较基本心理物理范式中结核和D型神经元的能力。当前，没有人工耳蜗网络模型使用生物学确定的突触动力学和连通性。我们旨在提供一种在生理上尽可能准确的模型，从而可以更深入地了解耳鸣，耳蜗植入和听觉处理。 公共卫生相关性：我们对听觉系统的理解推动了助听器和人工耳蜗的发展。目前，进展受到我们对听觉脑干中发生的处理的不良理解的限制。这项研究将确定听觉脑干电路的结构，并使用此信息来研究听觉信息处理。