Studies of the Cochlear Nucleus Granule Cell Domain

描述(申请人提供)：对声音的感知归因于中枢听觉系统内神经活动的模式。听觉系统通常被定义为一系列结构，这些结构直接或间接地连接到耳蜗。然而，声音的意义不仅取决于通过听觉系统调节的光谱和时间特征，还取决于动物过去的历史和行为状态。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。在这项应用中，我们计划研究非听觉投射到耳蜗核的性质，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整合多模式影响的关键部位。初步数据显示，躯体感觉、前庭、桥脑、网状和下行听觉投射进入颗粒细胞域。我们将使用顺行和逆行追踪方法，结合光学和电子显微镜来识别投射神经元及其回路，免疫细胞化学染色程序来揭示不同终末的化学成分，以及电生理记录技术来表征投射到该区域的神经元的反应特性。我们将应用纳米技术来探索可生物降解聚合物的使用，目标是为这项研究创造一系列新的神经元示踪剂。将配体连接到颗粒表面的可能性可以增强示踪剂的摄取，以选择性地靶向特定的神经元家族。这项研究的数据将为听觉系统中高度整合的结构的突触组织提供新的知识，并应有助于深入了解不同的神经系统如何塑造听力的编码过程。随着我们了解体感系统是如何调节听力的，我们将对躯体耳鸣有更深入的了解，这可能有助于设计治疗策略，并更好地了解耳鸣的一般情况。

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.