Inhibitory feedback in the avian auditory brainstem

鸟类听觉脑干的抑制反馈

• 批准号: 10677324
• 负责人: James Baldassano
• 金额: $ 3.46万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10677324
• 关键词: Acoustic Nerve; Action Potentials; Address; Adult; Afferent Neurons; Age; Anatomy; Auditory; Auditory system; Binaural; Birds; Brain; Brain Stem; Cell Nucleus; Cells; Cochlear Implants; Cochlear nucleus; Code; Collaborations; Communication; Confocal Microscopy; Contralateral; Cues; Data; Dendrites; Distal; Electrophysiology (science); Electroporation; Feedback; Foundations; Frequencies; Functional disorder; Goals; Hearing; Heterogeneity; Hyperactivity; Hyperacusis; Immunohistochemistry; In Vitro; Individual; Inhibitory Synapse; Iontophoresis; Ipsilateral; Membrane; Mental Depression; Microscopy; Nervous System; Neural Inhibition; Neurons; Pathway interactions; Pattern; Pharmacology; Phase; Phenotype; Physiological; Population; Presbycusis; Property; Quality of life; Research; Role; Sensory; Shapes; Speech Sound; Stimulus; Structure; Symptoms; Synapses; Synaptic Transmission; Techniques; Tinnitus; Training; auditory processing; career; cell type; experimental study; gamma-Aminobutyric Acid; hearing impairment; human old age (65+); inhibitory neuron; insight; nerve supply; neural circuit; postsynaptic; reconstruction; response; segregation; sound; speech processing; stem; success; superior olivary nucleus; translational therapeutics; virtual; voltage

PROJECT SUMMARY Auditory sensory processing requires neuronal communication via action potentials with precision in the order of microseconds. The nervous system achieves this precision by specializing intrinsic membrane properties and synaptic transmission, particularly neural inhibition. Neural inhibition sharpens sensory processing by increasing the selectivity of neurons to particularly salient stimuli and issues with neural inhibition are thought to underlie sensory problems such as tinnitus, hyperacusis, and age-related hearing loss (ARHL). In the avian auditory brainstem, inhibition stems virtually entirely from the superior olivary nucleus (SON). Neurons in SON receive excitatory input from two distinct, parallel circuits: the ipsilateral cochlear nucleus angularis (NA), which encodes intensity information from the auditory nerve, and from the ipsilateral coincidence-detecting nucleus laminaris (NL), which encodes binaural timing information from the cochlear nucleus magnocellularis (NM). Studies in vitro have demonstrated that there were 2 electrophysiological phenotypes, a single-spiking and a tonic firing response, in SON, however, preliminary data has revealed a third phenotype, a patterned tonic phenotypes. Increasing sound intensity increased phase-locking capabilities in a subset of nucleus laminaris neurons, indicating that there is potentially convergence from NA and NL in SON, however it has not been demonstrated. Importantly, Burger et al. (2005) demonstrated that SON neurons either project ipsilaterally to NA, NL, and the cochlear nucleus magnocellularis, or to the contralateral SON. However, it is unclear if these phenotypes underlie the divergent projections. Research has shown that inhibition increases the precision of timing neurons in NM and NL, but the effect on intensity coding in NA, which contains many different cell types, is less clear. Inhibitory terminals are heterogeneously expressed in NA, which some seemingly clustered on cell bodies and others on distal dendrites. The electrophysiological diversity in NA has been shown to exist along a spectrum of operating modes. It is unclear if the inhibitory terminals are related to the functional heterogeneity in NA, particularly in rate-coding neurons that are encode the dynamic range of spectral information for intensity coding. The goal of this project is to determine how neurons in SON fit into well characterized brainstem circuits and how they influence intensity coding neurons in the following two Specific Aims. Aim 1 – to use in vitro electrophysiology, synaptic stimulation, and neuronal reconstruction to determine how inputs are integrated in SON and the cell-type specific targets of divergent projections from SON neurons. Aim 2- use in vitro electrophysiology, immunohistochemistry, expansion microscopy, and confocal microscopy to determine how inhibitory terminals are expressed along specific NA neurons and how inhibition shapes intensity coding in NA. My results will provide insight into how circuits can utilize specialized inhibitory neurons for sensory processing, and how inhibition can shape spectrotemporal processing through its effect on intensity coding.

项目摘要 听觉感觉处理需要通过动作电位进行神经元通信，精确度为 微秒。神经系统通过专门化内在膜特性和突触特性来实现这种精确性。 传输，尤其是神经抑制。神经抑制通过增加选择性来锐化感觉处理， 神经元对特别突出的刺激和神经抑制的问题被认为是感觉问题的基础， 耳鸣、听觉过敏和年龄相关性听力损失（ARHL）。在鸟类的听觉脑干中， 完全来自上级橄榄核（SON）。SON中的神经元接受来自两个不同的、平行的 回路：同侧耳蜗角核（NA），编码来自听觉神经的强度信息， 以及来自同侧的一致性检测核（NL），其编码来自以下的双耳定时信息： 耳蜗大细胞核（NM）。体外研究表明，有2个电生理 表型，一个单一的尖峰和紧张性放电反应，在SON，然而，初步数据显示，第三个 表型，一种模式化的补药表型。增加声音强度增加了一个子集的锁相能力， 结果表明，在SON中，NA和NL之间存在潜在的会聚，但在SON中， 被证明。重要的是，Burger等人（2005）证明SON神经元要么投射到同侧NA， NL和耳蜗大细胞核，或对侧SON。然而，目前尚不清楚这些表型是否 构成了发散的投影。研究表明，抑制增加了NM中计时神经元的精确性 和NL，但对NA中的强度编码的影响，其中包含许多不同的细胞类型，是不太清楚。抑制 在NA中不均匀地表达末端，其中一些似乎聚集在细胞体上，而另一些聚集在远端细胞体上。 树突NA的电生理多样性已被证明存在沿着一系列的操作模式。是 不清楚抑制性终末是否与NA的功能异质性有关，特别是在速率编码神经元中 其编码用于强度编码的光谱信息的动态范围。这个项目的目标是确定 SON中的神经元如何适应表征良好的脑干回路，以及它们如何影响SON中的强度编码神经元。 有两个具体目标。目的1 -使用体外电生理学，突触刺激和神经元重建 以确定输入如何整合在SON中以及来自SON的发散投射的细胞类型特异性靶点 神经元目的2-使用体外电生理学、免疫组织化学、扩增显微镜和共聚焦显微镜 确定抑制性末梢如何沿沿着特定NA神经元表达以及抑制如何形成强度 编码为NA。我的研究结果将提供深入了解如何电路可以利用专门的抑制神经元的感觉 处理，以及抑制如何通过其对强度编码的影响来塑造频谱时间处理。