Long-lasting deficits induced by transient developmental hearing loss

 描述（由申请人提供）：耳聋研究的重点是确定永久性听力损失的长期后果。然而，听觉处理缺陷可以由儿童时期的短暂性听力损失引起。这些感知、言语和语言处理方面的缺陷在正常听力恢复后仍会持续很长时间。这些缺陷持续存在的一种解释是，短暂性听力损失导致CNS细胞特性的不可逆变化，这可能导致刺激编码退化。因此，本提案将评估这样一个前提，即发育期间的短暂、轻度听力损失会诱导与感觉和非感觉神经缺陷相关的行为缺陷。当沙鼠训练和执行听觉心理物理任务时，将遥测记录具有短暂性听力损失史的沙鼠的多个部位的听觉皮层反应。核心假设：伴随暂时性发育性听力损失的感知缺陷可归因于感觉处理的退化（例如，声学参数的编码）和非感觉机制（例如，在任务执行期间增加神经反应）。三个目标测试的预测出现从这个假设：目标1将确定是否有一个特定的发展时期，在此期间，感知技能容易受到短暂性听力损失;动物将饲养与双边耳塞开始在三个年龄范围之一。在所有情况下，将对两个听觉任务（振幅（AM）或调频（FM）深度检测）进行心理测量性能评估。在移除耳塞后，将通过ABR测量确认耳蜗功能正常。目标二：为了确定由短暂性听力损失引起的感知缺陷是否与退化的感觉表征相关，将在初级听觉皮层中植入电极阵列，并在对每只动物进行目标1中所述任务之一的训练和测试时，通过遥测记录神经反应。神经功能将直接与在相同试验中获得的心理功能进行比较，使我们能够确定感觉编码是否因短暂性听力损失而受损，以及受损程度是否可以解释个体动物的感知缺陷。目标3：为了确定由暂时性听力损失引起的感知缺陷是否与非感觉机制的破坏相关，我们将比较作为听力状态的函数的对相同声学参数的神经反应：在任务执行期间与在被动听力期间（即，动物不参与任务的时期）。这个实验将使我们能够确定非感觉机制是否与个体动物的感知缺陷程度相关。总之，这些目标将揭示是否存在一个发育期，在此期间，短暂性听力损失会破坏支持感知性能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对学习或改善新的听觉感知技能造成持久的障碍。

 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.