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 发育听力损失（HL）的实验研究通常集中于关键时期（CP） 感觉剥夺会永久破坏神经功能。但是，童年时代经常出现 出生后逐渐延伸到青春期，导致明显的知觉缺陷。 此外，这些缺陷的幅度随着未发现的HL的较长时间而增加。这表明这一点 CP结束后，听觉功能仍然容易受到HL的影响，并将HL持续时间视为关键 自变量。但是，在CP之后发生的发育HL的影响知之甚少。 因此，该提案的目的是研究HL对A期间神经和行为处理的影响 通过性成熟扩展的临床相关时期。将使用实验范式 允许一个人解析外围和中心机制：瞬态耳塞插入，当移除后，离开 在测试时，外围未损坏。该提议将解决以下核心假设 关键时期后引起的发育HL会破坏听觉皮层的细胞性质 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。特定的目标1将确定CP之后长时间HL是否诱导 破坏听觉感知。双侧耳塞将用于诱导HL在两个后年龄，从内部诱导HL CP或结束后，并通过性成熟延伸。耳塞去除并恢复正常后 使用振幅调制（AM）检测任务，将对听力学阈值，动物进行训练和测试 厌恶性GO/NOGO程序。 AM检测阈值将从心理测量功能和 比较HL动物和窝窝对照。听觉脑干的反应将收集到 确定长时间发育的HL是否引起听觉脑干的变化。具体目标2 将确定CP之后长时间HL是否诱导了听觉皮层细胞性质，从而改变 在检测任务中减少AM刺激的感觉编码。将获得全细胞记录 从听觉皮层层2/3锥体神经元，检查皮质突触和射击特性。听觉 皮质神经元反应将记录在长期植入的64个通道电极阵列中，以唤醒 - 行为动物执行AM检测任务。神经对AM的反应将用于计算神经学 可以直接将其与行为性能以及HL和对照动物之间的功能进行比较。 这些实验将共同揭示CNS细胞机制是否容易受到发展的影响 即使在CP结束后，剥夺也将提供对HL延伸到青春期的新理解。