权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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）：大脑不再被视为一个固定的系统，而是一个可塑的系统，它能适应相关刺激的最佳编码。在某些情况下，大脑可能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使人衰弱的疾病的例子，并且与中枢听觉系统内的异常音调重组有关。了解听觉系统中的音调可塑性如何发生，以及我们如何通过声学和/或电刺激大脑来诱导频率编码的适当变化以改善听力，这可能具有重要的临床意义。因此，长期的目标，拟议的研究是映射出的功能电路tonotopic可塑性。基于先前的研究，频率编码的可塑性变化发生在听觉通路的所有阶段，并且涉及上行和下行网络。然而，皮质和皮质下结构之间的详细功能组织，可以解释如何tonotopic可塑性实际上发生在中枢听觉系统仍然是未知的。作为识别音调可塑性的详细功能电路的第一步，拟议的研究将使用各种电生理技术来绘制从初级听觉皮层（A1）到下丘中央核（ICC）的功能和解剖投射模式。A1和ICC都显示出在使中央tonotopic重组中发挥关键作用。特别是，研究表明，A1神经元的最佳频率（BF）偏移在皮质下结构（包括ICC）内诱导类似的BF偏移。此外，ICC内的BF移位也被证明有助于A1内的BF移位。使用氯胺酮麻醉的豚鼠，所提议的研究将研究不同频率和A1等电位区的电刺激如何激活ICC的不同频率和等电位区，以开始理解A1 BF移位如何在ICC神经元内引起类似的移位。为了识别解剖投影模式，将使用逆向刺激的创新方法，其中离皮质神经元可以从其轴突末梢向后激活到其细胞体。该方法能够识别A1在整个ICC中的单突触投射与多突触投射。因此，在同一动物中，可以绘制出从A1到ICC的功能和解剖投影模式。此外，ICC神经元内的BF移位将使用条件反射范例（纯音刺激与BF匹配的A1区域的刺激配对）来诱导。然后可以评估A1到ICC激活模式是否以及如何随着ICC神经元的声学驱动响应模式随时间变化而改变。这些发现将开始确定潜在的音调可塑性的功能电路，可以指导未来的听力损失和耳鸣的刺激策略。此外，已开发的电生理学方法可以扩展到研究一般神经科学领域感兴趣的其他脑区。