Vulnerability to Hearing Loss After the Developmental Critical Period

发育关键期后容易出现听力损失

• 批准号: 9926076
• 负责人: Kelsey Anbuhl
• 金额: $ 0.56万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2020-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9926076
• 关键词: Address; Adolescence; Adult; Age; Animals; Auditory; Auditory Brainstem Responses; Auditory Perception; Auditory area; Auditory system; Behavioral; Bilateral; Binaural; Birth; Brain; Brain Stem; Childhood; Chronic; Cochlear Implants; Control Animal; Detection; Development; Earplug; Electrodes; Etiology; Excision; Functional disorder; Gerbils; Goals; Human; Impairment; Implant; Individual; Intervention; Language Disorders; Lead; Literature; Measures; Neuraxis; Neurons; Neurophysiology - biologic function; Newborn Infant; Otologic Surgical Procedures; Performance; Peripheral; Population; Preparation; Procedures; Property; Psychometrics; Recovery; Research; Screening Result; Sensory; Sensory Deprivation; Sexual Maturation; Slice; Speech; Stimulus; Structure; Synapses; System; Testing; Time; Training; Whole-Cell Recordings; awake; childhood hearing loss; clinically relevant; critical developmental period; critical period; deprivation; design; experience; experimental study; hearing impairment; hearing screening; hippocampal pyramidal neuron; middle ear; normal hearing; postnatal; relating to nervous system; remediation; response; restoration; skills; speech recognition

PROJECT SUMMARY Experimental studies of developmental hearing loss (HL) typically focus on a critical period (CP) during which sensory deprivation can permanently disrupt neural function. However, childhood HL often emerges progressively after birth and extends through adolescence, leading to significant perceptual deficits. Furthermore, the magnitude of these deficits increases with longer periods of undetected HL. This suggests that auditory function remains vulnerable to HL after a CP has ended, and implicates HL duration as the key independent variable. However, the impact of developmental HL that occurs after the CP is poorly understood. Therefore, the goal of this proposal is to study the effect of HL on neural and behavioral processing during a clinically relevant period that extends through sexual maturation. An experimental paradigm will be used that allows one to parse peripheral and central mechanisms: transient earplug insertion which, when removed, leave the periphery undamaged at the time of testing. This proposal will address the core hypothesis that developmental HL induced after the critical period can disrupt cellular properties in the auditory cortex when the duration is sufficiently long, thereby impairing auditory perception and cortical encoding. There are two experimental Aims. Specific Aim 1 will determine whether long duration HL induced after the CP permanently disrupts auditory perception. Bilateral earplugs will be used to induce HL at two postnatal ages, beginning within the CP or after it ends, and extending through sexual maturity. After earplug removal and recovery of normal audiometric thresholds, animals will be trained and tested on an amplitude modulation (AM) detection task using an aversive Go/Nogo procedure. AM detection thresholds will be measured from psychometric functions and compared between HL animals and littermate controls. Auditory brainstem responses will be collected to determine whether long duration developmental HL induces changes to the auditory brainstem. Specific Aim 2 will determine whether long duration HL induced after the CP alters auditory cortex cellular properties, thereby diminishing the sensory encoding of AM stimuli during a detection task. Whole-cell recordings will be obtained from auditory cortex layer 2/3 pyramidal neurons to examine cortical synaptic and firing properties. Auditory cortex neuron responses will be recorded from chronically implanted 64 channel electrode arrays as awake- behaving animals perform the AM detection task. Neural responses to AM will be used to calculate neurometric functions that can be directly compared to behavioral performance, as well as between HL and control animals. Together, these experiments will reveal whether CNS cellular mechanisms remain vulnerable to developmental deprivation even after the CP ends, and will provide a new understanding of HL that extends into adolescence.

项目摘要 发育性听力损失（HL）的实验研究通常集中在关键期（CP），在此期间， 感觉剥夺会永久性地破坏神经功能然而，童年HL经常出现 在出生后逐渐发展，并延伸到青春期，导致显著的知觉缺陷。 此外，这些缺陷的程度随着未检测到HL的时间延长而增加。这表明 听力功能在CP结束后仍然容易受到HL的影响，并暗示HL持续时间是关键 自变量然而，对CP后发生的发育性HL的影响知之甚少。 因此，本提案的目标是研究HL对神经和行为处理的影响， 临床相关的时期，通过性成熟延伸。将使用一个实验范例， 允许人们解析外周和中枢机制：短暂的耳塞插入，当移除时， 测试时外围未损坏。这一提议将解决核心假设， 在关键期后诱导的发育性HL可以破坏听觉皮层的细胞特性， 持续时间足够长，从而损害听觉感知和皮层编码。有两 实验目的具体目标1将确定CP后是否永久性诱导长时间HL 干扰听觉感知双侧耳塞将用于在两个出生后年龄诱导HL， CP或结束后，并通过性成熟延伸。耳塞取出后恢复正常 听力阈值，动物将接受振幅调制（AM）检测任务的训练和测试， 令人厌恶的Go/Nogo程序。AM检测阈值将从心理测量函数测量， HL动物和同窝对照之间的比较。将收集听觉脑干反应， 确定是否长期发展HL诱导听觉脑干的变化。具体目标2 将决定CP后诱导的长时间HL是否改变了听皮层细胞的特性，从而 在检测任务期间减少AM刺激的感觉编码。将获得全细胞记录 从听觉皮层2/3层锥体神经元观察皮层突触和放电特性。听觉 皮层神经元反应将从长期植入的64通道电极阵列记录为清醒时， 行为动物执行AM检测任务。对AM的神经反应将用于计算神经测量 可以直接与行为表现进行比较的功能，以及HL和对照动物之间的功能。 总之，这些实验将揭示中枢神经系统的细胞机制是否仍然容易受到发育的影响。 剥夺，即使在CP结束后，并将提供一个新的理解HL延伸到青春期。