Electrophysiological mapping of corticocollicular projections involved with tonot

与音调相关的皮质丘状投射的电生理图

基本信息

批准号：
8423401
负责人：
Hubert Hyungil Lim
金额：
$ 13.66万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2014-02-28
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The brain is no longer viewed as a fixed system but a plastic system that adapts itself to optimally code for relevant stimuli. In some cases, the brain can experience abnormal plasticity. Hearing loss and tinnitus are two examples of debilitating conditions that affect millions of Americans and have been linked to abnormal tonotopic reorganization within the central auditory system. Understanding how tonotopic plasticity occurs within the auditory system and how we can acoustically and/or electrically stimulate the brain to induce appropriate changes in frequency coding to improve hearing can have significant clinical implications. Thus the long-term objective of the proposed studies is to map out the functional circuitry underlying tonotopic plasticity. Based on previous studies, plastic changes in frequency coding occur at all stages of the auditory pathway and involves both ascending and descending networks. However, the detailed functional organization between cortical and subcortical structures that can explain how tonotopic plasticity actually occurs within the central auditory system is still unknown. As an initial step towards identifying the detailed functional circuitry underlying tonotopic plasticity, the proposed studies will use various electrophysiological techniques to map out the functional and anatomical projection patterns from the primary auditory cortex (A1) to the central nucleus of the inferior colliculus (ICC). Both A1 and ICC have shown to play crucial roles in enabling central tonotopic reorganization. In particular, studies have demonstrated that best frequency (BF) shifts in A1 neurons induce similar BF shifts within subcortical structures, including ICC. Furthermore, BF shifts within ICC have also shown to contribute to BF shifts within A1. Using ketamine-anesthetized guinea pigs, the proposed studies will investigate how electrical stimulation of different frequency and isofrequency regions of A1 activate different frequency and isofrequency regions of ICC to begin to understand how A1 BF shifts induce similar shifts within ICC neurons. To identify the anatomical projection patterns, an innovative approach using antidromic stimulation will be used in which corticofugal neurons can be activated backwards from their axon terminals to their cell bodies. This method enables identification of mono- versus poly-synaptic projections from A1 throughout ICC. Thus in the same animal it is possible to map out the functional and anatomical projection pattern from A1 to ICC. Furthermore, BF shifts within ICC neurons will be induced using a conditioning paradigm (pure tone stimulation paired with stimulation of a BF matched A1 region). It is then possible to assess if and how the A1-to-ICC activation pattern altered as the acoustic-driven response patterns of ICC neurons change over time. These findings will begin to identify the functional circuitry underlying tonotopic plasticity that can guide future stimulation strategies for hearing loss and tinnitus. Furthermore, the developed electrophysiological methods can be expanded to investigate other brain regions of interest to the general neuroscience field.

描述（由申请人提供）：大脑不再被视为固定系统，而是一种适应相关刺激的塑料系统。在某些情况下，大脑会经历异常的可塑性。听力损失和耳鸣是影响数百万美国人的两个衰弱状况的例子，并与中央听觉系统内的调整调整重组有关。了解听觉系统内的调整可塑性是如何发生的，以及我们如何进行声学和/或电刺激大脑以诱导频率编码的适当变化以改善听力的变化可能具有重大的临床意义。因此，拟议的研究的长期目标是绘制构图可塑性的功能电路。基于先前的研究，频率编码的塑性变化发生在听觉途径的所有阶段，涉及上升和下降网络。但是，皮质和皮层结构之间的详细功能组织可以解释中央听觉系统中如何实际发生Thonotopic可塑性。作为确定构想构图可塑性的详细函数电路的第一步，拟议的研究将使用各种电生理技术来绘制从主要听觉皮层（A1）到下部核糖核体（ICC）的中心核的功能和解剖学投影模式。 A1和ICC都显示在启用中央吨位重组中起着至关重要的作用。特别是，研究表明，A1神经元中的最佳频率（BF）变化会在包括ICC在内的皮层结构内诱导类似的BF移动。此外，ICC内的BF移动也已显示出有助于A1内的BF移动。拟议的研究使用氯胺酮 - 麻醉的豚鼠，将研究A1的不同频率和同频区域的电刺激如何激活ICC的不同频率和同源区域，以开始了解A1 BF在ICC神经元内诱导类似的移位。为了识别解剖学投影模式，将使用一种使用抗刺激的创新方法，其中可以将皮质增生神经元从轴突末端向后激活至其细胞体。该方法可以识别来自ICC的A1的单突触投影。因此，在同一动物中，可以从A1到ICC绘制功能和解剖投影模式。此外，ICC神经元内的BF移位将使用条件范式（纯音刺激与BF匹配的A1区域匹配）诱导。然后，可以评估随着ICC神经元的声学驱动响应模式随时间变化，A1至ICC激活模式是否会改变。这些发现将开始识别基础塑料可塑性的功能电路，该电路可以指导未来的听力损失和耳鸣的刺激策略。此外，可以扩展开发的电生理方法以研究一般神经科学领域感兴趣的其他大脑区域。