Neuromodulation in the auditory system

听觉系统的神经调节

• 批准号: 9198445
• 负责人: DAVID J PERKEL
• 金额: $ 38.07万
• 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/9198445
• 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 study; Genetically Engineered Mouse; Hearing; Individual; Inferior Colliculus; Injection of therapeutic agent; Link; Location; Membrane; Mus; Neurodegenerative Disorders; Neurons; Parkinson Disease; Patients; Pharmacology; Physiological; Property; Receptor Activation; Research; Role; Shapes; Signal Transduction; Site; Slice; Social Environment; Source; Speech; Staining method; Stains; Stimulus; Structure; Synapses; Synaptic Transmission; System; Testing; Tracer; Tyrosine 3-Monooxygenase; Whole-Cell Recordings; auditory pathway; auditory processing; 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

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：理解语音取决于听觉系统准确表示突出声音的能力。这种表达可能会被各种因素改变，包括涉及神经调节系统的疾病。例如，帕金森氏病患者有语音处理问题，这表明多巴胺改变了这些突出信号的正常表达。拟议的研究集中在多巴胺的作用，在改变代表性的声音在下丘（IC）。IC是调制显著信号的听觉处理的主要位置，因为它接收来自多个听觉和非听觉源的输入，它包含多巴胺受体和纤维，并且来自该提议的初步数据表明多巴胺调制IC听觉反应。这个建议的目的是确定多巴胺改变IC中发声表征的机制。第一个目标将使用在清醒小鼠的IC中应用药理学试剂的体内单单位记录，以确定多巴胺受体激活对发声反应的影响。第二个目标将使用小鼠IC脑切片的全细胞记录来确定多巴胺对不同神经元类型的内在和突触特性的影响。第三个Aim将使用体内全细胞记录 以确定不同神经元类型的内在属性如何塑造对发声的选择性。因此，目标1-3将提供对复杂声音听觉反应的细胞和突触机制的综合理解。第四个目标将确定多巴胺能输入IC的来源，这是理解引起多巴胺释放到IC的行为背景的重要一步。这一建议的意义在于，它是第一个 综合研究多巴胺对细胞，突触和电路特性的影响，这些特性是突出声音的IC反应的基础。这些结果将增加我们对有意义声音的听觉处理的机械理解，以及这种编码如何随着不同的社会背景，生理状态和沟通障碍而变化。这些使用听力正常小鼠的研究将促进未来对基因工程小鼠的研究，以进一步探索特定交流和神经系统疾病的机制。