Regulation of excitability in a sensory system by cellular and network components

通过细胞和网络组件调节感觉系统的兴奋性

• 批准号: 9527902
• 负责人: SHOBHANA SIVARAMAKRISHNAN
• 金额: $ 33.14万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9527902
• 关键词: Acoustics; Adult; Affect; Anatomy; Animals; Architecture; Area; Auditory; Auditory area; Auditory system; Automobile Driving; Behavior; Brain; Brain Stem; C57BL/6 Mouse; CBA/Ca Mouse; Cell Nucleus; Characteristics; Code; Complex; Data; Distant; Dorsal; Ear; Electrophysiology (science); Feedback; Frequencies; Functional disorder; Future; Gated Ion Channel; Goals; Hearing; Hearing problem; Income; Inferior Colliculus; Inherited; Injection of therapeutic agent; Interneurons; Ion Channel; Ion Channel Gating; Label; Laboratories; Maps; Measures; Membrane; Midbrain structure; Movement; Mus; Neurons; Pathology; Pattern; Play; Population; Principal Investigator; Process; Recruitment Activity; Recurrence; Regulation; Role; Shapes; Signal Transduction; Slice; Source; Structure; Synapses; Synaptic Potentials; Testing; Work; auditory nuclei; auditory pathway; awake; base; cell type; experimental study; improved; in vivo; neuromechanism; optical imaging; programs; receptive field; response; sensory system; sound; sound frequency; spatiotemporal; stellate cell; synaptic inhibition; tool; translational impact; vocalization; voltage

Program Director/Principal Investigator (Last, First, Middle): Sivaramakrishnan, Shobhana ABSTRACT The long-term goal of this work is to improve understanding of the neural mechanisms that underlie hearing. To determine how acoustic information is processed by the brain, it is critical to elucidate how sound frequency is represented at different sound levels. This project focusses on the central nucleus of the inferior colliculus (ICC), the auditory nucleus in the midbrain that is critically important in regulating hierarchical processing of acoustic information between the ear and the auditory cortex. For its role in hearing, the ICC receives ascending inputs from most parts of the brainstem and is influenced by descending projections from the auditory cortex. In addition, it contains complex local circuits and unique cell types. Recent work demonstrates that local feedback circuitry in the ICC creates acoustically relevant codes despite inadequate brainstem input. This project aims to understand the mechanisms by which the ICC codes the frequency content of simple and complex sounds. Experiments are based on the broad hypothesis that the representation of frequency by the ICC depends on the spatio-temporal characteristics of its local circuits. Aim 1 will identify structure-function correlates of local circuitry and examine connectivity within and across frequency laminae. We will use electrophysiological recordings and optical imaging in brain slices to identify the mechanisms by which the two principal cell types in the ICC, disc-shaped and stellate cells, interact to generate a map of frequencies. Aim 2 will identify how local circuits contribute to frequency representation of simple sounds. In vivo electrophysiological recordings from the ICC of awake mice will be used to examine the contribution of local circuitry and voltage-gated ion channels to the receptive fields of ICC neurons. Aim 3 will identify how local circuits contribute to frequency representation of vocalizations, which are complex natural sounds. In vivo electrophysiological recordings from awake mice will be used to examine the cellular basis for an overrepresentation of high frequencies in the ICC, and the selectivity of neurons to vocalizations with different frequency content. Dysfunction of the ICC plays a critical role in hearing abnormalities. By examining how the arrangement of local circuitry in the ICC contributes to its importance in transforming frequency information from lower auditory nuclei, our work will lay the groundwork for the mechanisms that underlie the frequency re-organization in the ICC that accompanies auditory pathology and will identify the components of hearing disorders that originate in the lower brainstem, midbrain, or higher regions of the auditory hierarchy. 1

项目负责人/主要研究者（最后，第一，中间）：Sivaramakrishnan，Shobhana 摘要 这项工作的长期目标是提高对听力神经机制的理解。到 确定声音信息是如何被大脑处理的，关键是要阐明声音频率是如何变化的。 在不同的声音水平。本项目的重点是下丘中央核（ICC）， 中脑中的听觉核，在调节声音的分级处理中至关重要 耳朵和听觉皮层之间的信息。由于其在听觉中的作用，ICC接收来自 脑干的大部分区域，并受到听觉皮层下行投射的影响。此外还 包含复杂的局部电路和独特的细胞类型。最近的工作表明，局部反馈电路在 ICC创建声学相关的代码，尽管脑干输入不足。 这个项目的目的是了解的机制，其中ICC编码的频率内容的简单和 复杂的声音实验基于广泛的假设，即ICC对频率的表征 取决于其局部电路的时空特性。目标1将确定结构-功能相关性 的局部电路和检查连接内和跨频率层。我们将使用电生理学 记录和光学成像，以确定脑组织中两种主要细胞类型的机制。 ICC，盘状和星状细胞，相互作用产生频率图。目标2将确定本地电路如何 有助于简单声音的频率表示。ICC的体内电生理记录 清醒的小鼠将被用于检查局部电路和电压门控离子通道对脑缺血的贡献。 ICC神经元的感受野目标3将确定本地电路如何对 发声，这是复杂的自然声音。来自清醒小鼠的体内电生理学记录将被记录。 用于检查ICC中高频率过度表现的细胞基础，以及 神经元对不同频率成分的发声的反应。 ICC的功能障碍在听力异常中起着关键作用。通过研究如何安排当地的 ICC中的电路有助于其在转换来自较低听觉核的频率信息中的重要性， 我们的工作将为国际刑事法院频率重组的基础机制奠定基础， 伴随着听觉病理学，并将确定听力障碍的组成部分，起源于低 脑干、中脑或听觉层次的更高区域。 1