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，可能会导致心理困扰和 运动受损。主动声音定位，或者在聆听时移动头部，就是一种行为的例子 将双耳的听觉输入与头部位置的输入相结合（NIDCD 优先领域 1： 洞察力）。事实上，单侧听力损失或植入人工耳蜗的人可以利用头部运动来 补偿紊乱的听觉输入。了解中枢听觉通路如何整合听觉 输入头部位置信号将有助于我们研究人们如何在行为和神经上适应和 应对前庭和听觉障碍。 主动声音定位的小鼠模型将增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，例如寻找丢失的物品 幼崽通过哭声来判断。此外，还有强大的遗传、生理和成像工具包 可用于剖析小鼠神经回路功能的工具。尽管有所有这些优点，但还没有模型 小鼠主动声音定位。该项目将填补这一空白。 该提案的具体目标是确定小鼠如何将头部与声音对齐，以便 将其本地化。我的假设是听觉皮层将听觉输入与头部位置信号结合起来，以实现 这种行为。该提案的核心创新是将大规模神经记录与高 自由行为的分辨率分析，使我能够了解神经元群体的活动如何介导 适应性行为反应。在目标 1 中，我将确定小鼠用于对齐的策略和大脑区域 他们的头有声音。在目标 2 中，我将确定听觉皮层中的神经元如何编码头部运动和 将其与声音结合起来。总的来说，这些研究将阐明激活声音的神经回路 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，这是一家领先的 R1 研究机构，拥有互动式研究中心 神经科学界和丰富的智力和技术资源。我是终身教职助理 埃默里大学教授，拥有自己独立的实验室空间和设备。我聘请了一名全职研究人员 专家协助这些研究，我能够培训神经科学、生物医学的研究生 工程学和医学博士/博士课程。我将接受两位顾问的指导：Robert Froemke 博士，位于 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学方面的专家。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项目 指导自然行为并赋予对混乱的恢复力的途径。