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 理解语音取决于听觉系统准确表示的能力 显着的声音。这种表示可能会因各种因素而改变，包括疾病 涉及神经调节系统。例如，帕金森氏病患者患有 语音处理问题表明多巴胺会改变这些的正常表示 显着信号。拟议的研究集中于多巴胺在改变的作用 下丘（IC）中的显着声音。 IC是调节听觉的主要位置 处理明显信号是因为它从多个听觉和非审计中接收输入 来源，它包含多巴胺受体和纤维，以及该提案的初步数据 表明多巴胺调节IC听觉响应。该提议的目的是 确定多巴胺改变IC中发声的表示的机制。 第一个目的将使用药理学的体内单位记录 清醒小鼠IC中的药物确定多巴胺受体激活对 对发声的响应。第二个目标将使用鼠标IC大脑中的全细胞记录 切片以确定多巴胺对不同的内在和突触特性的影响 神经元类型。第三个目标将使用体内全细胞记录来确定固有的方式 不同神经元类型的特性对发声的选择性形成了选择性。目标1-3将 提供对细胞和突触机制的综合理解 听觉对复杂声音的响应。第四目标将决定 对IC的多巴胺能输入，这是了解行为环境的重要一步 这种引起多巴胺释放到IC中。 该提议的意义在于，它是对影响的第一次综合研究 IC对明显反应的细胞，突触和电路特性上的多巴胺 听起来。结果将增加我们对听觉处理的机械理解 有意义的声音以及这种编码如何随着不同的社会环境而变化 国家和沟通障碍。这些研究使用正常听力的小鼠将 促进对基因工程小鼠的未来研究，以进一步探测机制 基本的特定沟通和神经系统疾病。