Circuit mechanisms underlying temporal processing in auditory cortex

听觉皮层时间处理的电路机制

• 批准号: 10058263
• 负责人: Michael Wehr
• 金额: $ 51.45万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10058263
• 关键词: Acoustics; Affect; Animals; Auditory; Auditory area; Auditory system; Behavior; Behavioral; Cells; Chemosensitization; Code; Communication; Complex; Comprehension; Computer Models; Crowding; Detection; Discrimination; Elderly; Emotional; Feedback; Fright; Goals; Hearing; Human; Inferior Colliculus; Interneurons; Lesion; Measures; Mediating; Modeling; Mus; Neurons; Noise; Parvalbumins; Pharmacology; Population; Presbycusis; Process; Psychometrics; Reaction Time; Reporting; Research; Restaurants; Role; Shapes; Shock; Somatostatin; Speech; Speech Discrimination; Speech Sound; Stream; Structure; Testing; Time; Transgenic Organisms; Viral; Voice; age related; awake; cell type; cholinergic; classical conditioning; cognitive task; conditioned fear; experimental study; hippocampal pyramidal neuron; human old age (65+); inhibitory neuron; insight; neural circuit; neurophysiology; operation; optogenetics; predictive modeling; public health relevance; rapid detection; relating to nervous system; response; sound; speech processing; synaptic inhibition; theories

Project Summary Over half of those over 65 years old have age-related hearing loss, and the primary communication challenge reported by older adults is difficulty understanding speech in noisy conditions, such as a crowded restaurant. Age-related speech processing deficits can occur even with completely normal audiometric hearing, and are instead associated with temporal processing deficits in central structures such as auditory cortex. The mechanisms underlying temporal processing in auditory cortex are not well understood. Our broad goal is to elucidate these mechanisms. We will use a well-established measure of temporal processing in both humans and animals: the ability to detect a brief gap in background noise. The circuitry underlying gap detection in cortex remains unknown. In Aim 1 we seek to elucidate this circuitry by combining neuronal recording and optogenetics in awake mice performing a gap detection task. In Aim 2 we seek to understand how gap detection is enhanced when fear conditioning confers emotional significance to the gap. We propose to use fear potentiation of gap detection in mice as a model for how associative learning in auditory cortex assigns meaning to temporally structured sounds such as speech. We will use neuronal recording and optogenetics before, during, and after fear conditioning to determine the cortical circuit mechanisms underlying the associative learning of temporal structure. In both aims, our hypotheses are expressed as a candidate neural circuit model which makes specific predictions. In each Aim we will test these predictions, using the results to refine the model. Our broad goal is to understand which cortical neurons and circuits are necessary for gap detection and fear potentiation of gap detection, and how the dynamics of these circuits mediate these processes. Achieving this goal will provide fundamental new insights into the mechanisms underlying temporal processing, and how alterations of these mechanisms could contribute to age-related deficits in speech comprehension.

项目摘要 超过一半的65岁以上的人患有与年龄相关的听力损失， 据报道，老年人的沟通挑战是在嘈杂的环境中难以理解言语。 例如拥挤的餐厅。可能会出现与听力相关的语音处理缺陷 即使是完全正常的听力测定听力， 听觉皮层等中枢结构的处理缺陷。的机制 听觉皮层中时间处理还没有被很好地理解。我们的主要目标是阐明 这些机制。我们将使用一个公认的时间处理措施，在这两个 人类和动物：能够在背景噪音中检测到短暂的间隙。所述电路 皮层中潜在的间隙检测仍然未知。在目标1中，我们试图阐明这种电路 通过结合神经元记录和光遗传学在清醒的小鼠进行间隙检测， 任务在目标2中，我们试图了解当恐惧条件反射时，间隙检测是如何增强的。 赋予了差距情感上的意义。我们建议使用恐惧增强的差距检测 作为听觉皮层中的联想学习如何将意义分配给 时间结构化的声音，如语音。我们将使用神经元记录和光遗传学 之前，期间，和之后的恐惧条件反射，以确定皮层电路机制 时间结构的联想学习。在这两个目标中，我们的假设是 表示为做出特定预测的候选神经电路模型。在每个目标中，我们 将测试这些预测，使用结果来完善模型。我们的主要目标是了解 哪些皮层神经元和回路是间隙检测和间隙恐惧增强所必需的 检测，以及这些电路的动态如何调解这些过程。实现这一目标 将为时间处理机制提供基本的新见解， 这些机制的改变如何导致与年龄相关的言语缺陷 理解力