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降解的听觉经验对大脑功能的影响，这些变化发生的机制以及这些知识如何有助于开发有效的补救策略。以导电性听力损失（CHL）的形式下降的听力（例如，吸收的中耳炎）是美国儿童中最常见的疾病，并且与听觉感知过程的缺陷反复有关，这些疾病已经解决了导电损失后多年的持续存在。为了更好地了解这些持久的处理缺陷的基础机制，我们利用了一种可逆CHL的技术，可以精确控制发育听力损失的时间和双边表达。提出的实验将将CHL的历史与单个神经元反应特性的可塑性及其协调的排列相关联。最初的实验将改变CHL发作的年龄，以描绘下丘，内侧遗传体和原发性听觉皮层中双耳加工的敏感周期调节。持续研究将比较单侧与双侧CHL对中脑和前脑核的功能组织的影响，并确定一旦恢复正常听力的可塑性方面，而持续的可塑性方面与那些逐渐消失。第二项研究将对听觉皮层中对单膜和双耳刺激选择性的经验依赖性影响进行全面评估。这些研究将记录在醒着动物中单个神经元水平的声音，信噪比，时间包膜变化以及时间差和时间差异中的编码中的可塑性。通过记录关键的“现实世界”变量，例如CHL的时机，CHL的双边模式以及无CHL听力的长度会影响开发的中央听觉系统，这些研究进一步为医疗保健从业人员提供了有关与儿童chl的各种干预策略相关的成本和收益的信息。这些实验将进一步了解经验如何塑造大脑功能和行为。拟议的工作将研究经验在介导双耳听力的脑电路中的启发性作用。通过将可逆导电性听力损失与技术相结合，以表征在单个神经元和听觉中脑和前脑核中代表性图的可塑性，提出的研究提出了一种有希望的方法来解决有关经验依赖性可塑性和与儿童听力丧失病理学相关的经验依赖性可塑性和转移问题的基础研究问题。