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

• 批准号: 8230575
• 负责人: Hubert Hyungil Lim
• 金额: $ 14.38万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/8230575
• 关键词: Acoustic Stimulation; Acoustics; Adult; Affect; American; Animals; Auditory; Auditory area; Auditory system; Behavioral; Brain; Brain Stem; Brain region; Cavia; Cell Nucleus; Clinical; Code; Data; Dimensions; Electric Stimulation; Frequencies; Future; Goals; Hearing; Implant; Inferior Colliculus; Ketamine; Learning; Link; Maps; Methods; Midbrain structure; Modeling; Mono-S; Neurons; Neurosciences; Outcome; Output; Pattern; Performance; Plastics; Play; Positioning Attribute; Presynaptic Terminals; Property; Psychological reinforcement; Reporting; Resolution; Role; Site; Speech Perception; Staging; Stimulus; Structure; Synapses; System; Techniques; Thalamic structure; Time; Tinnitus; auditory pathway; base; conditioning; experience; hearing impairment; improved; innovation; insight; interest; neuronal cell body; prevent; public health relevance; relating to nervous system; response

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. PUBLIC HEALTH RELEVANCE: In the U.S., approximately 36 million adults have reported hearing loss with about 40,000 receiving auditory implants and approximately 2 million people have reported debilitating tinnitus. Both tinnitus and poor speech perception with implants have been linked to abnormal frequency coding within the central auditory system. Thus the clinical goal of our proposed studies is to better understand how to acoustically and/or electrically activate the auditory system to improve frequency coding properties important for speech perception or tinnitus suppression.

描述（由申请人提供）：大脑不再被视为一个固定的系统，而是一个可调整的系统，它可以适应相关刺激的最佳编码。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种使人衰弱的疾病，它们与中枢听觉系统异常的张力重组有关。了解听觉系统中的张力异位可塑性是如何发生的，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来改善听力，具有重要的临床意义。因此，提出的研究的长期目标是绘制出功能电路下的张力塑性。根据以往的研究，频率编码的可塑性变化发生在听觉通路的各个阶段，包括上升和下降网络。然而，皮层和皮层下结构之间的详细功能组织，可以解释如何在中枢听觉系统中实际发生张力变性仍然是未知的。作为确定声位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）的功能和解剖投影模式。A1和ICC都显示出在使中心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）移位在皮层下结构（包括ICC）中诱导了类似的BF移位。此外，ICC内的BF移位也显示有助于A1内的BF移位。使用氯胺酮麻醉的豚鼠，这些研究将研究A1的不同频率和同频区域的电刺激如何激活ICC的不同频率和同频区域，从而开始了解A1 BF位移如何在ICC神经元内诱导类似的位移。为了识别解剖投影模式，将使用一种创新的方法，使用反向刺激，在这种方法中，皮质神经元可以从轴突末端向后激活到它们的细胞体。这种方法能够在ICC中识别A1的单突触和多突触投影。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，使用条件反射模式（纯音刺激与BF匹配的A1区刺激配对）可以诱导ICC神经元内的BF移位。然后，就有可能评估a1到ICC的激活模式是否以及如何随着ICC神经元的声驱动响应模式随时间的变化而改变。这些发现将开始确定音调可塑性的功能电路，可以指导未来听力损失和耳鸣的刺激策略。此外，开发的电生理方法可以扩展到研究一般神经科学领域感兴趣的其他大脑区域。