Long-lasting deficits induced by transient developmental hearing loss

 描述(申请人提供)：耳聋研究的重点一直是确定永久性听力损失的长期后果。然而，儿童时期的一过性听力损失可能会导致听觉处理障碍。这些在感知、言语和语言处理方面的缺陷在正常听觉恢复后会持续很长一段时间。这些缺陷持续存在的一种解释是，短暂性听力损失会导致中枢神经系统细胞特性的不可逆转变化，这可能导致刺激编码的退化。因此，该提案将评估这样一个前提，即发育过程中短暂、轻微的听力损失会导致与感觉神经和非感觉神经缺陷相关的行为障碍。来自多个地点的听觉皮质反应将从沙土鼠的远程测量中记录下来，这些沙土鼠在训练和执行听觉心理物理任务时有暂时性听力损失的历史。核心假设：伴随着短暂性发育性听力损失的知觉缺陷既可归因于感觉处理的退化(例如，声学参数的编码)，也可归因于非感觉机制(例如，在任务执行过程中神经反应的增加)。这一假设产生了三个目标测试预测：目标1将确定是否存在一个特定的发育时期，在此期间感知技能容易受到短暂性听力损失的影响；动物将在三个年龄段中的一个年龄段开始使用双侧耳塞饲养。在所有情况下，心理测量的表现将通过两项听觉任务进行评估，即幅度(AM)或调频(FM)深度检测。摘除耳塞后，ABR测试将确认耳蜗功能正常。目的2：为了确定短暂性听力损失引起的知觉障碍是否与感觉表征的退化有关，将在初级听觉皮质植入一个电极阵列，当每只动物接受目标1中描述的任务之一的训练和测试时，神经反应将被遥测记录。神经测量功能将直接与相同试验中获得的心理测量功能进行比较，从而使我们能够确定感觉编码是否因短暂性听力损失而受损，以及损害的程度是否可以解释单个动物的知觉缺陷。目的3：为了确定短暂性听力损失引起的知觉障碍是否与非感觉机制的中断有关，我们将比较相同声学参数的神经反应作为听状态的函数：在任务执行期间和在被动听期间(即动物不参与任务的时间段)。这项实验将使我们能够确定非感官机制是否与个体动物的知觉缺陷的大小相关。总之，这些目标将揭示是否存在一个发育期，在此期间，短暂性听力损失扰乱了支持知觉表现的感觉和非感觉机制的成熟。这意味着，持续的神经处理缺陷可能会给学习或提高新的听觉感知技能带来持久的障碍。

 DESCRIPTION (provided by applicant): The emphasis of deafness research has been to establish the long-term consequences of permanent hearing loss. However, auditory processing deficits can be induced by transient hearing loss during childhood. These deficits in perception, speech, and language processing can persist long after normal audibility is restored. One explanation for the persistence of these deficits is that transient hearing loss causes irreversibl changes to CNS cellular properties that may lead to degraded stimulus encoding. Therefore, this proposal will evaluate the premise that transient, mild hearing loss during development induces behavioral deficits that are associated with sensory and non-sensory neural deficits. Auditory cortex responses from multiple sites will be recorded telemetrically from gerbils with a history of transient hearing loss as they train on, and perform, auditory psychophysical tasks. The core hypothesis: Perceptual deficits that accompany transient developmental hearing loss are attributable both to degraded sensory processing (e.g., encoding of acoustic parameters) and non-sensory mechanisms (e.g., increased neural response during task performance). Three aims test predictions emerging from this hypothesis: Aim 1 will determine whether there is a specific developmental epoch during which perceptual skills are vulnerable to transient hearing loss; animals will be reared with bilateral earplugs beginning during one of three age ranges. In all cases, psychometric performance will be assessed on two auditory tasks, amplitude (AM) or frequency modulation (FM) depth detection. Normal cochlear function will be confirmed with ABR measurements following earplug removal. Aim 2: To determine whether perceptual deficits induced by transient hearing loss are associated with a degraded sensory representation, an electrode array will be implanted in the primary auditory cortex, and neural responses will be recorded telemetrically as each animal is trained and tested on one of the tasks described in Aim 1. Neurometric functions will be compared directly to psychometric functions obtained during the same trials, permitting us to establish whether sensory encoding is impaired by transient hearing loss, and whether the magnitude of impairment could explain the perceptual deficits of individual animals. Aim 3: To determine whether the perceptual deficits induced by transient hearing loss is correlated with disruption of a non-sensory mechanism, we will compare neural responses to identical acoustic parameters as a function of listening state: during task performance versus during passive listening (i.e., a period when animals are not engaged in a task). This experiment will permit us to establish whether a non-sensory mechanism is correlated with the magnitude of perceptual deficits within individual animals. Together, these Aims will reveal whether there is a developmental period during which transient hearing loss disrupts the maturation of sensory and non-sensory mechanisms that support perceptual performance. The implication is that persistent neural processing deficits may present an enduring barrier to learning or improving on novel auditory perceptual skills.