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Auditory Cortex Plasticity and Tinnitus

听觉皮层可塑性和耳鸣

基本信息

批准号：
8220710
负责人：
Brian Allman
金额：
$ 15.62万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
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：
2011-02-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8220710
关键词：
Acoustic Stimulation Acoustics Adult Affect Animal Housing Animal Model Animals Auditory Auditory area Behavior assessment Behavioral Body Surface Chronic Clinical Cochlea Complex Disease Ear Environment Equilibrium Esthesia Evaluation Exposure to Frequencies General Population Head and neck structure Hearing Hearing Aids High-Frequency Hearing Loss Housing Human Investigation Lesion Loudness Maps Neurons Noise Noise-Induced Hearing Loss Partial Hearing Loss Patients Perception Pharmaceutical Preparations Physiologic pulse Play Process Rattus Rehabilitation therapy Reporting Residual state Role Series Stimulus Techniques Time Tinnitus Treatment Efficacy Work auditory pathway base behavior measurement behavior test cochlear lesion deafness deprivation extracellular hearing impairment ototoxicity prevent public health relevance relating to nervous system research study somatosensory sound theories

项目摘要

DESCRIPTION (provided by applicant): Tinnitus, a subjective perception of a phantom auditory sensation (e.g., ringing in the ears), affects approximately 10-15% of the general population. At present, there is no cure, and there are no drugs known that suppress the disorder. Tinnitus, in its chronic form, is most often associated with noise-induced hearing loss. Although the underlying mechanism(s) of tinnitus remain elusive, it is well established that hearing loss alters the balance of excitation and inhibition throughout the central auditory pathway, ultimately leading to cortical plasticity. Examples of cortical plasticity observed in animal models include a reorganization of the tonotopic map following a frequency-specific cochlear lesion (i.e., intramodal cortical plasticity), and in the case of profound deafness caused by ototoxicity, neurons in the auditory cortex becoming responsive to somatosensory stimulation (i.e., crossmodal cortical plasticity). It has been proposed that tinnitus emerges as a negative consequence of intramodal cortical plasticity following hearing loss; however, the intramodal cortical plasticity theory of tinnitus has not been investigated thoroughly as no studies have performed both cortical electrophysiological recordings and a behavioral assessment of tinnitus in the same animals. Furthermore, given that approximately two-thirds of human patients suffering from tinnitus can modulate its pitch and loudness by somatosensory stimulation of their head and neck (termed "somatic tinnitus"), it is reasonable to predict that, in addition to tonotopic map reorganization, crossmodal cortical plasticity may be involved in the disorder. Thus, this proposal will investigate, for the first time, the relationship between chronic tinnitus and auditory cortex plasticity (intra- and crossmodal) caused by noise-induced hearing loss. To that end, electrophysiological recording will be used to assess the responsiveness of neurons in the primary auditory cortex of adult rats to auditory and somatosensory stimulation 45 days after monaural exposure to high- frequency noise. To determine which noise-exposed rats develop chronic tinnitus, behavioral testing with a gap pre-pulse inhibition acoustic startle paradigm will be used, and the results will be correlated with the electrophysiological findings. It is hypothesized that only a subset of noise-exposed rats will show both intra- and crossmodal cortical plasticity and that such changes correlate with behavioral evidence of tinnitus. Moreover, it is predicted that the crossmodal cortical plasticity will be characterized by neurons that respond to somatosensory stimulation of the rostral body surface (i.e., head and neck). A second series of experiments will determine if cortical plasticity and behavioral evidence of tinnitus can be suppressed by housing rats in an acoustically-enriched environment for one month. The rationale for this rehabilitation is based on recent studies on hearing-impaired animals and humans which suggest that intramodal cortical plasticity can be offset by chronic acoustic stimulation at the specific frequencies associated with the hearing loss. The efficacy of this treatment approach (sound therapy) has not been evaluated using animals with behavioral evidence of tinnitus. PUBLIC HEALTH RELEVANCE: Tinnitus, a subjective perception of a phantom auditory sensation (e.g., ringing in the ears), affects approximately 10-15% of the general population. Using an animal model in which tinnitus and hearing loss are induced by extremely loud noise, this proposal will determine if tinnitus results from intramodal and/or crossmodal plasticity in the auditory cortex induced by monaural hearing loss, and whether an enriched acoustic environment can suppress tinnitus by reversing the noise-induced cortical plasticity.

描述(申请人提供)：耳鸣，一种幻听的主观感觉(例如，耳鸣)，影响大约10%-15%的普通人群。目前，还没有治愈的方法，也没有已知的抑制这种疾病的药物。耳鸣，其慢性形式，最常与噪音引起的听力损失有关。尽管耳鸣的潜在机制(S)仍不清楚，但众所周知，听力损失会改变中枢听觉通路中兴奋和抑制的平衡，最终导致皮质可塑性。在动物模型中观察到的皮质可塑性的例子包括频率特定的耳蜗病后紧张性映射的重组(即，模式内皮质可塑性)，以及在由耳毒性引起的深度耳聋的情况下，听觉皮质中的神经元对躯体感觉刺激(即，跨模式皮质可塑性)产生反应。已经提出耳鸣是听力损失后模式内皮质可塑性的负面后果，然而，耳鸣的模式内可塑性理论还没有得到深入的研究，因为还没有研究在同一动物中同时进行皮质电生理记录和耳鸣的行为评估。此外，鉴于大约三分之二的人类耳鸣患者可以通过对其头部和颈部的躯体感觉刺激来调节其音调和响度(称为躯体耳鸣)，因此可以合理地预测，除了调幅图重组外，跨模式皮质可塑性可能参与了这种疾病。因此，这项提议将第一次调查慢性耳鸣和由噪声导致的听力损失引起的听觉皮质可塑性(内模式和跨模式)之间的关系。为此，将使用电生理记录来评估成年大鼠在单耳暴露于高频噪声45天后，初级听觉皮质神经元对听觉和躯体感觉刺激的反应。为了确定哪些噪声暴露的大鼠会患上慢性耳鸣，将使用GAP预脉冲抑制声惊厥范式的行为测试，并将结果与电生理结果相关联。据推测，只有一部分暴露在噪声中的大鼠会同时表现出模式内和跨模式的皮质可塑性，并且这种变化与耳鸣的行为证据相关。此外，据预测，交叉模式皮层的可塑性将由对吻侧体表(即头和颈部)的体感刺激做出反应的神经元来表征。第二系列实验将确定是否可以通过将老鼠安置在声学丰富的环境中一个月来抑制大脑皮层的可塑性和耳鸣的行为证据。这种康复的基本原理是基于最近对听力受损动物和人类的研究，这些研究表明，与听力损失相关的特定频率的慢性声刺激可以抵消模式内皮质可塑性。这种治疗方法(声音疗法)的有效性还没有在有耳鸣行为证据的动物身上进行评估。与公共卫生相关：耳鸣是一种幻听的主观感觉(例如，耳鸣)，影响大约10%-15%的一般人口。利用极强噪声诱发耳鸣和听力损失的动物模型，该方案将确定耳鸣是否由单耳听力损失引起的听觉皮质的模式内和/或跨模式可塑性所致，以及丰富的声环境是否可以通过逆转噪声诱导的皮质可塑性来抑制耳鸣。