The Role of Central Gain Control in Hyperacusis of Diverse Origin

中央增益控制在不同来源的听觉过敏中的作用

• 批准号: 9263685
• 负责人: Benjamin D Auerbach
• 金额: $ 6.04万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9263685
• 关键词: Affect; Amygdaloid structure; Animal Model; Animals; Anxiety Disorders; Auditory; Auditory Evoked Potentials; Auditory area; Auditory system; Basic Science; Behavior; Behavioral; Behavioral Assay; Brain; Brain region; Chronic; Clinical; Clinical Sciences; Disease; Electrodes; Electrophysiology (science); Enhancers; Etiology; Exhibits; FMR1; Fragile X Syndrome; Frequencies; Functional disorder; General Population; Hearing; High Prevalence; Hyperactive behavior; Hyperacusis; Hypersensitivity; Impairment; Implant; Inferior Colliculus; Inherited; Lateral; Link; Loudness; Loudness Perception; Measurement; Measures; Mental Depression; Modeling; Neurodevelopmental Disorder; Neurons; Noise; Operant Conditioning; Pain; Peripheral; Pharmaceutical Preparations; Pharmacology; Population; Process; Rattus; Reaction Time; Risk Factors; Role; Sensorineural Hearing Loss; Sensory; Sensory Disorders; Signal Transduction; Testing; Tinnitus; Training; Vigabatrin; Williams Syndrome; Work; auditory processing; autism spectrum disorder; behavior measurement; economic impact; experimental study; hearing impairment; insight; metabotropic glutamate receptor 5; multi-electrode arrays; nervous system disorder; neural circuit; neural correlate; novel; public health relevance; relating to nervous system; response; sound; synaptic function; therapy development; treatment effect; treatment strategy

 DESCRIPTION (provided by applicant): Hyperacusis is a prevalent sensory disorder in which sounds of moderate intensity are perceived as intolerably loud or even painful. Despite the significant societal and economic impact of hyperacusis, treatments for this disorder are lacking. While hearing loss has consistently been identified as the primary risk factor for hyperacusis, many other disorders are also associated with loudness intolerance, suggesting the causes of hyperacusis can be varied. Hyperacusis is particularly prevalent in several neurodevelopmental disorders, such as Williams Syndrome, Fragile X Syndrome (FX), and autism spectrum disorders (ASD). The aim of this proposal is to directly compare the mechanisms underlying hyperacusis of distinct origin to determine if there is a shared neural disruption that manifests a auditory hypersensitivity. Specifically, the proposed work will test the hypothesis that altered central gain control is a common pathophysiological mechanism in two distinct models of hyperacusis: long-term hearing loss and an animal model of FX, the leading inherited cause of ASD. A combination of electrophysiological and behavioral measures will be used to characterize the relationship between central auditory hyperactivity and hyperacusis-like behavior in these models to: (1) determine the neural correlates of hyperacusis due to hearing loss; (2) characterize hyperacusis and the potential neural correlates in an animal model of FX; and (3) identify drugs that may ameliorate measures of hyperacusis in both hearing loss and FX models. Understanding how these distinct forms of hyperacusis are similar and/or different will provide both clinical and basic science insights relevant to understanding and treating hyperacusis.

 描述（由申请人提供）：听觉过敏是一种普遍的感觉障碍，其中中等强度的声音被认为是难以忍受的响亮甚至疼痛。尽管听觉过敏症对社会和经济有重大影响，但缺乏对这种疾病的治疗。虽然听力损失一直被认为是听觉过敏的主要危险因素，但许多其他疾病也与响度不耐受有关，这表明听觉过敏的原因可能是多种多样的。听觉过敏在几种神经发育障碍中特别普遍，例如威廉姆斯综合征、脆性X综合征（FX）和自闭症谱系障碍（ASD）。该建议的目的是直接比较不同起源的听觉过敏的潜在机制，以确定是否有一个共同的神经中断，表现出听觉超敏反应。具体来说，拟议的工作将测试的假设，改变中央增益控制是一个共同的病理生理机制，在两个不同的模型的听觉过敏：长期听力损失和FX的动物模型，ASD的主要遗传原因。电生理学和行为测量的组合将用于表征这些模型中中枢听觉过度活跃和听觉过度样行为之间的关系，以：（1）确定由于听力损失引起的听觉过度的神经相关性;（2）表征FX动物模型中的听觉过度和潜在的神经相关性;以及（3）确定可以改善听力损失和FX模型中的听觉过敏测量的药物。了解这些不同形式的听觉过敏是如何相似和/或不同的，将提供与理解和治疗听觉过敏相关的临床和基础科学见解。