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.

项目概要 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 感觉剥夺会永久破坏神经功能。然而，儿童时期的 HL 经常出现 出生后逐渐出现并持续到青春期，导致显着的知觉缺陷。 此外，这些缺陷的严重程度随着未被发现的 HL 时间的延长而增加。这表明 CP 结束后，听觉功能仍然容易受到 HL 的影响，并且暗示 HL 持续时间是关键 自变量。然而，人们对 CP 之后发生的发育性 HL 的影响知之甚少。 因此，本提案的目标是研究 HL 对神经和行为处理过程中的影响。 临床相关的时期一直延伸到性成熟。将使用一个实验范式 允许人们解析外围和中枢机制：短暂的耳塞插入，当移除时，会留下 测试时外围未损坏。该提案将解决以下核心假设： 关键期后诱导的发育性 HL 会破坏听觉皮层的细胞特性，当 持续时间足够长，从而损害听觉感知和皮质编码。有两个 实验目标。具体目标 1 将确定 CP 后是否会永久诱发长持续时间 HL 扰乱听觉感知。将使用双侧耳塞在出生后两个年龄诱导 HL，从 20 岁开始 CP 或结束后，并延伸至性成熟。拔掉耳塞后恢复正常 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 检测阈值将根据心理测量函数进行测量， HL 动物和同窝对照动物之间进行比较。将收集听觉脑干反应 确定长期发育性 HL 是否会引起听觉脑干的变化。具体目标2 将确定 CP 改变听觉皮层细胞特性后是否诱导长持续时间 HL，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 来自听觉皮层 2/3 锥体神经元的信号，用于检查皮层突触和放电特性。听觉 皮层神经元反应将通过长期植入的 64 通道电极阵列记录为清醒状态 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学 可以直接与行为表现以及 HL 和对照动物之间进行比较的功能。 总之，这些实验将揭示中枢神经系统细胞机制是否仍然容易受到发育的影响。 即使在 CP 结束后，我们仍会感到剥夺，并将提供对 HL 的新理解，并将其延伸到青春期。