Activity-Dependent Influences on Auditory Circuits

对听觉回路的活动依赖性影响

• 批准号: 8471096
• 负责人: Daniel B. Polley
• 金额: $ 35.73万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-09-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8471096
• 关键词: Address; Affect; Age; Animal Experimentation; Animals; Architecture; Auditory; Auditory Perceptual Disorders; Auditory area; Auditory system; Basic Science; Behavior; Bilateral; Brain; Cell Nucleus; Characteristics; Chemosensitization; Child; Childhood; Cochlea; Conductive hearing loss; Contralateral; Costs and Benefits; Data; Development; Diagnosis; Disadvantaged; Ear; Exhibits; Frequencies; Functional disorder; Goals; Healthcare; Hearing; Inferior Colliculus; Intervention; Investigation; Ipsilateral; Knowledge; Lead; Length; Life; Maps; Medial geniculate body; Mediating; Methods; Midbrain structure; Neurons; Noise; Otitis Media with Effusion; Otolaryngologist; Pattern; Plastics; Predisposition; Procedures; Process; Property; Prosencephalon; Rattus; Recording of previous events; Regulation; Relative Risks; Research; Role; Sensory; Sensory Deprivation; Signal Transduction; Staging; Stimulus; Techniques; Testing; Thalamic structure; Time; United States; Variant; Work; age related; awake; binaural hearing; brain shape; computerized data processing; density; deprivation; experience; hearing impairment; infancy; receptive field; reconstruction; remediation; research study; response; senescence; sensory system; sound

DESCRIPTION (provided by applicant): The overall goal of the proposed research is to better understand the impact of degraded auditory experience on brain function, the mechanisms by which these changes occur, and how such knowledge can contribute to the development of effective remediation strategies. Degraded hearing in the form of conductive hearing loss (CHL) such as otitis media with effusion is the most commonly diagnosed illness among children in the United States and has been repeatedly associated with deficits in auditory perceptual processes that persist for years after the conductive loss has been resolved. To better understand the mechanisms underlying these enduring processing deficits, we have utilized a technique for reversible CHL that permits precise control over the timing and bilateral expression of developmental hearing loss. The proposed experiments will relate a history of CHL to plasticity of single neuron response properties and their coordinated arrangement into functional maps. Initial experiments will vary the age of CHL onset to delineate the sensitive period regulation of binaural processing in the inferior colliculus, medial geniculate body and primary auditory cortex. Continuing studies will compare the effects of unilateral versus bilateral CHL on the functional organization of midbrain and forebrain nuclei and identify the aspects of plasticity that endure versus those that fade away once normal hearing has been restored. A second line of research will provide a comprehensive assessment of experience-dependent influences on monaural and binaural stimulus selectivity in the auditory cortex. These studies will document plasticity in the encoding of sound spectra, signal-to-noise ratio, temporal envelope variations as well as interaural level and time differences at the level of the single neuron in the awake animal. By documenting how critical "real-world" variables such as the timing of CHL, the bilateral pattern of CHL and the length of CHL-free hearing impact the developing central auditory system, these studies further inform health care practitioners about the costs and benefits associated with various intervention strategies for childhood CHL. These experiments will further our understanding of how experience shapes brain function and behavior. The proposed work will examine the instructive role of experience in the formation of brain circuits that mediate binaural hearing. By combining a method for reversible conductive hearing loss with techniques to characterize plasticity at the level of single neurons and representational maps in auditory midbrain and forebrain nuclei, the proposed studies introduce a promising approach to address basic research questions regarding experience-dependent plasticity and translational questions related to the pathophysiology of childhood hearing loss.

描述(由申请人提供)：拟议研究的总体目标是更好地了解听觉体验退化对大脑功能的影响，这些变化发生的机制，以及这些知识如何有助于制定有效的补救策略。以传导性听力损失(CHL)的形式表现的听力下降，如渗出性中耳炎，是美国儿童中最常见的诊断疾病，并一再与听觉感知过程缺陷有关，这种缺陷在传导性听力损失得到解决后持续多年。为了更好地了解这些持久的加工缺陷背后的机制，我们利用了一种可逆的CHL技术，它允许精确控制发育性听力损失的时间和双边表达。拟议的实验将把CHL的历史与单个神经元反应属性的可塑性以及它们在功能图谱中的协调排列联系起来。初步实验将改变CHL的发病年龄，以描绘双耳加工在下丘、内侧膝状体和初级听觉皮质的敏感期调节。继续的研究将比较单侧和双侧CHL对中脑和前脑核团功能组织的影响，并确定一旦恢复正常听力，持续和消失的可塑性方面。第二条线的研究将全面评估经验依赖对听觉皮质中单耳和双耳刺激选择性的影响。这些研究将记录清醒动物单个神经元水平上的声谱编码、信噪比、时间包络变化以及耳间水平和时间差的可塑性。通过记录关键的“真实世界”变量，如CHL的时机、CHL的双边模式和无CHL的听力持续时间如何影响发育中的中枢听觉系统，这些研究进一步向卫生保健从业者提供了与儿童CHL的各种干预策略相关的成本和收益。这些实验将进一步加深我们对经验如何塑造大脑功能和行为的理解。这项拟议的工作将检验经验在调节双耳听力的大脑回路形成中的指导作用。通过将可逆性传导性听力损失的方法与在单个神经元水平上表征可塑性的技术和听觉中脑和前脑核团的代表性图谱相结合，拟议的研究引入了一种有希望的方法来解决与儿童听力损失的病理生理学相关的基础研究问题和翻译问题。