Studies of the Cochlear Nucleus Granule Cell Domain

描述（由申请人提供）：声音感知归因于中枢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连接到耳蜗的一系列结构。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性，还取决于动物的过去历史和行为状态。换句话说，声音处理还应该包括非听觉系统，这些系统将传达感觉运动功能、情感、学习和记忆。在这个应用程序中，我们计划研究耳蜗核的非听觉投射的性质，以深入了解不同的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域是多模态影响整合的关键部位。初步数据显示，躯体感觉，前庭，脑桥，网状和下行听觉投射访问颗粒细胞域。我们将使用顺行和逆行道跟踪方法结合光学和电子显微镜，以确定投射神经元和他们的电路，免疫细胞化学染色程序，以揭示不同终端的化学，和电生理记录技术，以表征神经元投射到这个区域的响应特性。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。将配体附着到颗粒表面的可能性可以增强示踪剂摄取，以选择性靶向特定的神经元家族。这项研究的数据将提供有关听觉系统中高度整合结构的突触组织的新知识，并应深入了解不同的神经系统如何塑造听觉编码过程。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和更好地了解耳鸣。

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.