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

项目主任/首席调查员(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基础神经机制的理解。至 确定大脑如何处理声音信息，关键是要阐明声音频率是如何 以不同的音级表示。本项目的重点是下丘中央核(ICC)。 中脑中的听觉核团，在调节声学的分级处理中起着至关重要的作用 耳朵和听觉皮质之间的信息。由于其在听证中的作用，国际刑事法院从 脑干的大多数部分，并受到听觉皮质下行投射的影响。此外，它还 包含复杂的本地电路和独特的单元类型。最近的研究表明，大脑中的局部反馈电路 尽管脑干输入不足，ICC还是创建了与声音相关的代码。 本项目旨在了解ICC对Simple和SIMPLE和 复杂的声音。实验是基于一个广泛的假设，即ICC对频率的表示 取决于其本地电路的时空特性。目标1将确定结构与功能之间的关联 并检查频率层内和频率层之间的连通性。我们将使用电生理学 脑片上的记录和光学成像以确定大脑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。来自国际刑事法院的活体电生理记录 清醒的小鼠将被用来检查局部电路和电压门控离子通道对 ICC神经元的感受野。目标3将确定本地电路如何对频率表示做出贡献 发声，这是复杂的自然声音。清醒小鼠的体内电生理记录将是 用于检查ICC中高频过度表示的细胞基础，以及 神经元对不同频率成分的发声反应。 ICC功能障碍在听力异常中起着至关重要的作用。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团的频率信息方面的重要性， 我们的工作将为国际刑事法院频率重组所依据的机制奠定基础 伴随着听觉病理学，并将确定起源于低位的听力障碍的组成部分 脑干、中脑或听觉层次的高级区域。 1

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