Central auditory pathways for integrating auditory input with head position during active sound localization in mice

在小鼠主动声音定位过程中将听觉输入与头部位置整合的中枢听觉通路

• 批准号: 10652787
• 负责人: Christopher Rodgers
• 金额: $ 19.26万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10652787
• 关键词: 3-Dimensional; Affect; Animals; Area; Auditory; Auditory Physiology; Auditory area; Auditory system; Behavior; Behavioral; Biomedical Engineering; Brain; Brain region; Child; Cochlear Implants; Communities; Compensation; Complex; Coupling; Crying; Data; Disease; Doctor of Philosophy; Ear; Electrophysiology (science); Environment; Equipment; Future; Genetic; Goals; Head; Head Movements; Hearing; Hearing problem; Human Resources; Imaging Device; Individual; Institution; Learning; Left; Link; Location; Machine Learning; Measures; Mediating; Modeling; Monitor; Motion; Motor; Mus; National Institute on Deafness and Other Communication Disorders; Neurons; Neurosciences; New York; Perception; Persons; Physiological; Play; Population; Positioning Attribute; Posture; Recording of previous events; Recovery; Research; Resolution; Resources; Role; Scanning; Sensory; Sensory Disorders; Side; Signal Transduction; Somatosensory Cortex; Sound Localization; Source; Specialist; Speech; Stimulus; Techniques; Testing; Training; United States; Universities; Variant; Visual Cortex; Work; auditory pathway; behavioral response; career; coping; design; ear infection; empowerment; equilibration disorder; free behavior; graduate student; hearing impairment; improved; innovation; motor impairment; mouse model; neural; neural circuit; neuroprosthesis; neurotransmission; optogenetics; professor; programs; psychological distress; pup; rehabilitation strategy; resilience; response; sound; tenure track

Hearing and balance disorders are widespread in the US and can cause psychological distress and impaired movement. Active sound localization, or moving the head while listening, is an example of a behavior that integrates auditory input from both ears with input about head position (NIDCD Priority Area 1: Perception). Indeed, people with single-sided hearing loss or cochlear implants can use head motion to compensate for disordered auditory input. Understanding how central auditory pathways integrate auditory input with head position signals would help us study how people can behaviorally and neurally adapt to and cope with vestibular and auditory disorders. A mouse model of active sound localization would advance our understanding of the neural circuitry of active sound localization. Mice naturally rely on hearing to find sound sources, such as seeking out their lost pups by the sound of their cries. Moreover, there is a powerful toolkit of genetic, physiological, and imaging tools available to dissect neural circuit function in mice. Despite all these advantages, there are no models of active sound localization in mice. This project will fill that gap. The specific objective of this proposal is to determine how mice align their heads with sound in order to localize it. My hypothesis is that auditory cortex integrates auditory input with head position signals to enable this behavior. The central innovation of this proposal is to unite large-scale neural recordings with high- resolution analysis of free behavior, enabling me to understand how activity in populations of neurons mediates adaptive behavioral responses. In Aim 1, I will identify the strategies and brain regions that mice use to align their heads with sound. In Aim 2, I will determine how neurons in the auditory cortex encode head motion and integrate it with sound. Collectively, these studies will elucidate the neural circuitry that enables active sound localization, and lay the groundwork for future work to understand how this circuitry confers resilience to hearing loss. I will perform this research at Emory University, a leading R1 research institution with an interactive neuroscience community and abundant intellectual and technical resources. I am a tenure-track Assistant Professor at Emory, with my own independent lab space and equipment. I have hired a full-time research specialist to assist in these studies, and I am able to train graduate students from Neuroscience, Biomedical Engineering, and the MD/PhD program. I will receive guidance from two consultants: Dr. Robert Froemke at New York University and Dr. Robert Liu at Emory. Both are experts in auditory physiology and behavior. This support will empower me to direct an independent research program on the distributed processing in auditory pathways that direct natural behavior and confer resilience to disorder.

听力和平衡障碍在美国很普遍，会导致心理痛苦和 行动不便。主动声音定位，或在倾听时移动头部，就是一种行为 其将来自两只耳朵的听觉输入与关于头部位置的输入相结合(NIDCD优先区域1： 感知)。事实上，单侧听力损失或植入人工耳蜗的人可以使用头部运动来 补偿无序的听觉输入。了解中枢听觉通路如何整合听觉 头部位置信号的输入将帮助我们研究人们如何在行为和神经上适应和 处理前庭和听觉障碍。 主动声音定位的小鼠模型将促进我们对神经回路的理解 主动声音定位。老鼠天生依靠听觉来寻找声源，比如寻找丢失的声源 幼崽通过它们的叫声来判断。此外，还有一个强大的遗传、生理和成像工具包 可用于解剖小鼠神经回路功能的工具。尽管有所有这些优势，但还没有模式 主动声在小鼠体内的定位。这个项目将填补这一空白。 这项建议的具体目标是确定小鼠如何将头与声音对齐，以便 本地化。我的假设是，听觉皮质将听觉输入与头部位置信号相结合，从而使 这种行为。这一建议的中心创新是将大规模的神经记录与高质量的 自由行为的分辨率分析，使我能够理解神经元群体中的活动如何调节 适应性行为反应。在目标1中，我将确定小鼠用来排列的策略和大脑区域 他们的头上有声音。在目标2中，我将确定听觉皮质中的神经元如何编码头部运动和 把它和声音结合起来。总而言之，这些研究将阐明使主动声音成为可能的神经回路 本地化，并为未来的工作奠定基础，以了解该电路如何赋予弹性 听力损失。 我将在埃默里大学进行这项研究，该大学是一家领先的R1研究机构，拥有一个互动 神经科学界和丰富的智力和技术资源。我是一名终身教职助理 埃默里大学的教授，有我自己的独立实验室空间和设备。我雇了一名全职研究人员 我有专门的专家来协助这些研究，我能够培训神经科学、生物医学的研究生 工程学，以及医学博士项目。我将接受两位顾问的指导：罗伯特·弗罗梅克博士 纽约大学和埃默里大学的罗伯特·刘博士。两人都是听觉生理学和行为方面的专家。这 支持将使我能够指导一个关于听觉分布式处理的独立研究计划 引导自然行为并赋予无序韧性的途径。