Studies of the Cochlear Nucleus Granule Cell Domain

耳蜗核颗粒细胞域的研究

• 批准号: 7240478
• 负责人: DAVID K. RYUGO
• 金额: $ 33.84万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7240478
• 关键词: Acoustics; Affective; Air; Animals; Arousal; Auditory; Auditory area; Auditory system; Behavioral; Binding; Brain; Cell Nucleus; Cervical spinal cord structure; Characteristics; Chemistry; Clinical; Cochlea; Cochlear nucleus; Code; Collaborations; Cues; Data; Detection; Dyes; Ear; Electron Microscopy; Electrons; Emotions; External Ear; Family; Goals; Grant; Head; Hearing; Inferior Colliculus; Injection of therapeutic agent; Investigation; Knowledge; Learning; Ligands; Light; Localized; Mediating; Memory; Methods; Microscopic; Modality; Motion; Nature; Neurons; Neurotransmitter Receptor; Neurotransmitters; Numbers; Operative Surgical Procedures; Organism; Pattern; Personal Satisfaction; Polymers; Pontine structure; Positioning Attribute; Procedures; Process; Property; Proprioception; Rattus; Recording of previous events; Relative (related person); Research; Sensorimotor functions; Series; Shapes; Site; Skeletal muscle structure of neck; Sound Localization; Source; Spinal; Staining method; Stains; Structure; Structure of nucleus cuneatus; Surface; Synapses; System; Techniques; Technology; Testing; Time; Tinnitus; Tracer; Trigeminal Nuclei; Vestibular Nerve; Work; biodegradable polymer; cell type; dorsal cochlear nucleus; external ear auricle; granule cell; insight; interest; nanoparticle; particle; receptor; relating to nervous system; response; somatosensory; sound; therapy design; uptake; vibration; visual information

DESCRIPTION (provided by applicant): Perception of sound is attributed to the pattern of neural activity within the central auditory system. The auditory system is typically defined as a series of structures that are connected directly or indirectly to the cochlea. The significance of a sound, however, depends not only on spectral and temporal characteristics as mediated through the auditory system, but also on the past history and behavioral state of the animal. In other words, sound processing should also include non-auditory systems that would convey sensorimotor functions, emotion, learning, and memory. In this application, we plan to study the nature of non-auditory projections to the cochlear nucleus in order to gain insight into how different systems influence our perception of sound. We propose that the granule cell domain of the cochlear nucleus represents a key site for the integration of mutimodal influences. Preliminary data reveals that somatosensory, vestibular, pontine, reticular, and descending auditory projections access the granule cell domain. We will use anterograde and retrograde tract tracing methods in conjunction with light and electron microscopy to identify projecting neurons and their circuits, immunocytochemical staining procedures to reveal the chemistry of the different terminals, and electrophysiological recording techniques to characterize the response properties of neurons projecting to this region. We will apply nanoparticle technology to explore the use of biodegradable polymers with the goal of creating a new line of neuronal tracers for this study. The possibility of attaching ligands to the surface of the particles could enhance tracer uptake for the selective targeting of specific families of neurons. The data from this research will provide new knowledge on the synaptic organization of a highly integrative structure in the auditory system, and should yield insights into how diverse neural systems shape the coding process for hearing. As we learn about how the somatosensory system modulates hearing, we will gain insight into somatic tinnitus that could contribute to the design of treatment strategies and a better understanding of tinnitus in general.

描述（由申请人提供）：声音的感知归因于中央听觉系统内的神经活动模式。听觉系统通常被定义为直接或间接与耳蜗相连的一系列结构。然而，声音的意义不仅取决于通过听觉系统介导的频谱和时间特征，还取决于动物的过去历史和行为状态。换句话说，声音处理也应该包括传递感觉运动功能、情感、学习和记忆的非听觉系统。在这项应用中，我们计划研究耳蜗核非听觉投射的本质，以深入了解不同系统如何影响我们对声音的感知。我们认为，耳蜗核的颗粒细胞结构域是整合多模态影响的关键部位。初步数据显示，体感、前庭、脑桥、网状和下行听觉投射进入颗粒细胞区域。我们将使用顺行和逆行神经束追踪方法，结合光镜和电子显微镜来识别突起的神经元及其回路，使用免疫细胞化学染色程序来揭示不同末端的化学成分，使用电生理记录技术来表征突起到该区域的神经元的响应特性。我们将应用纳米颗粒技术来探索生物可降解聚合物的使用，目的是为这项研究创造一种新的神经元示踪剂。将配体附着在颗粒表面的可能性可以增强示踪剂的摄取，从而选择性靶向特定的神经元家族。这项研究的数据将提供关于听觉系统中高度整合结构的突触组织的新知识，并应该深入了解不同的神经系统如何塑造听觉的编码过程。当我们了解躯体感觉系统如何调节听力时，我们将深入了解躯体耳鸣，这可能有助于设计治疗策略并更好地了解耳鸣。