Neuromodulation in the auditory system

听觉系统的神经调节

基本信息

批准号：
9402597
负责人：
DAVID J PERKEL
金额：
$ 32.34万
依托单位：
WASHINGTON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-01-14 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9402597
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 Injections 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 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

项目摘要

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再现显着声音的能力。这种表现可能会因多种因素而改变，包括涉及神经调节系统的疾病。例如，帕金森病患者存在言语处理问题，这表明多巴胺改变了这些显着信号的正常表达。拟议的研究重点是多巴胺在改变下丘（IC）中显着声音的表现中的作用。 IC 是调节显着信号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，并且该提案的初步数据表明多巴胺调节 IC 听觉反应。该提案的目的是确定多巴胺改变 IC 发声表征的机制。第一个目标将使用体内单单位记录，并在清醒小鼠的 IC 中应用药物制剂，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 脑切片中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。第三个目标将使用体内全细胞记录以确定不同神经元类型的内在特性如何影响发声的选择性。因此，目标 1-3 将提供对复杂声音听觉反应背后的细胞和突触机制的综合理解。第四个目标将确定 IC 多巴胺能输入的来源，这是理解引发多巴胺释放到 IC 的行为环境的重要一步。这个提案的意义在于它是第一个综合研究多巴胺对 IC 对显着声音反应的细胞、突触和电路特性的影响。研究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有助于未来对基因工程小鼠的研究，以进一步探讨特定沟通和神经系统疾病的机制。