Neuromodulation in the auditory system

听觉系统的神经调节

• 批准号: 8630806
• 负责人: DAVID J PERKEL
• 金额: $ 33.41万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-14 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8630806
• 关键词: Acoustics; Affect; Agonist; Attention; Auditory; Auditory Perceptual Disorders; Auditory system; Behavioral; Brain; Brain region; Code; Communication impairment; Complex; Data; Disease; Dopamine; Dopamine Agonists; Dopamine Receptor; Environment; Fiber; Future; Genetic; Genetically Engineered Mouse; Hearing; Individual; Inferior Colliculus; Injection of therapeutic agent; Link; Location; Membrane; Mus; Neurodegenerative Disorders; Neurons; Parkinson Disease; Patients; Physiological; Process; Property; Receptor Activation; Research; Role; Shapes; Signal Transduction; Site; Slice; Social Environment; Source; Speech; Staining method; Stains; Stimulus; Structure; Synapses; Synaptic Transmission; System; Testing; Time; Tracer; Tyrosine 3-Monooxygenase; Whole-Cell Recordings; auditory pathway; awake; cell type; improved; in vivo; nerve supply; nervous system disorder; neural circuit; neurophysiology; neuroregulation; public health relevance; receptor; relating to nervous system; response; sound; speech processing; vocalization

Project Summary Understanding speech depends on the capacity of the auditory system to accurately represent salient sounds. This representation may be altered by a variety of factors, including disorders involving neuromodulatory systems. For example, patients with Parkinson's disease have speech processing problems suggesting that dopamine alters normal representation of these salient signals. The proposed studies focus on the role of dopamine in altering representation of salient sounds in the inferior colliculus (IC). The IC is a prime location for modulating auditory processing of salient signals because it receives input from multiple auditory and non-auditory source, it contains dopamine receptors and fibers, and preliminary data from this proposal indicate that dopamine modulates IC auditory responses. The objective of this proposal is to determine the mechanisms by which dopamine alters the representation of vocalizations in IC. The first Aim will use in vivo single unit recordings with application of pharmacological agents in the IC of awake mice to determine the effects of dopamine receptor activation on responses to vocalizations. The second Aim will use whole-cell recordings in mouse IC brain slices to determine the effects of dopamine on intrinsic and synaptic properties of different neuron types. The third Aim will use in vivo whole-cell recordings to identify how intrinsic properties of different neuron types shape selectivity to vocalizations. Aims 1-3 will thus provide an integrated understanding of the cellular and synaptic mechanisms underlying auditory responses to complex sounds. The fourth Aim will determine the sources of dopaminergic input to the IC, an important step towards understanding the behavioral contexts that elicit dopamine release into the IC. The significance of this proposal is that it is the first integrated study of the effects of dopamine on the cellular, synaptic and circuit properties underlying IC responses to salient sounds. The results will increase our mechanistic understanding of auditory processing of meaningful sounds and how this encoding changes with different social contexts, physiological states and communication disorders. These studies using mice with normal hearing will facilitate future studies of genetically engineered mice to further probe the mechanisms underlying specific communication and neurological disorders.

项目摘要 理解语言依赖于听觉系统准确表达的能力 很明显的声音。这种表现可能会被各种因素改变，包括疾病 涉及神经调节系统。例如，帕金森氏症患者有 语音处理问题表明多巴胺改变了这些神经元的正常表达 显著的信号。建议的研究集中在多巴胺在改变 下丘(IC)有明显的声音。IC是调节听觉的最佳位置 显著信号的处理，因为它接收来自多个听觉和非听觉的输入 来源，它包含多巴胺受体和纤维，以及这项提议的初步数据 表明多巴胺调节IC听觉反应。这项建议的目的是 确定多巴胺改变IC发声表现的机制。 第一个目标是使用活体单一单位记录，并应用药理学 清醒小鼠IC中药物测定多巴胺受体激活对脑内神经递质的影响 对发声的反应。第二个目标是使用小鼠IC脑中的全细胞记录 脑片以确定多巴胺对不同脑区内源性和突触特性的影响 神经元类型。第三个目标将使用活体全细胞记录来确定 不同神经元类型的特性决定了对发声的选择性。目标1-3将因此 提供对潜在的细胞和突触机制的综合理解 对复杂声音的听觉反应。第四个目标将确定 中枢多巴胺能输入，是了解行为背景的重要一步 这会导致多巴胺释放到IC中。 这项建议的意义在于，它是第一次对 多巴胺对中枢神经系统显著反应的细胞、突触和电路特性的影响 听起来。这一结果将增加我们对听觉加工的机械理解 有意义的声音以及这种编码如何随着不同的社会背景、生理环境和 状态和沟通障碍。这些研究使用的是听力正常的小鼠 促进未来对基因工程小鼠的研究，以进一步探索其机制 潜在的特定沟通和神经障碍。