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.

项目总结 听觉感觉处理需要通过动作电位进行神经元交流，其精度约为 微秒。神经系统通过专门化固有的膜特性和突触来达到这种精确度。 传递，尤其是神经抑制。神经抑制通过增加选择性增强感觉加工 神经元对特别显著的刺激和神经抑制的问题被认为是感觉问题的基础，如 耳鸣、听力亢进和年龄相关性听力损失(ARHL)。在鸟类的听觉脑干中，抑制实际上是 完全来自上橄榄核(SON)。SON中的神经元接受来自两个不同的、平行的 环路：同侧耳蜗角核(NA)，它编码来自听神经的强度信息， 和来自同侧的符合检测板状核(NL)，它编码来自 耳蜗核大细胞(NM)。体外研究表明，有两种电生理学。 然而，在SON中，初步数据显示了第三种表型，即单峰和紧张性激发反应。 表型，一种有花纹的滋补表型。声音强度的增加增强了以下部分的锁相能力 板层核神经元，提示SON内可能存在NA和NL的会聚现象 已经被证明了。重要的是，Burger等人。(2005)证明SON神经元或者同侧投射到NA， NL和耳蜗核的大细胞，或对侧子。然而，目前还不清楚这些表型是否 这是两种不同的预测的基础。研究表明，抑制提高了NM中计时神经元的精确度 和NL，但在NA中对强度编码的影响不太清楚，NA包含许多不同的细胞类型。抑制性 末端在NA中异质性地表达，一些似乎聚集在细胞体上，另一些聚集在远端 树枝状结构。NA中的电生理多样性已被证明存在于一系列操作模式中。它是 尚不清楚抑制性终末是否与NA，特别是速率编码神经元的功能异质性有关 其对用于强度编码的光谱信息的动态范围进行编码。这个项目的目标是确定 SON中的神经元如何与特征明确的脑干环路相匹配，以及它们如何影响大脑中的强度编码神经元。 遵循两个具体目标。目的1-使用体外电生理学、突触刺激和神经元重建 确定输入如何在SON中整合以及SON发散投射的细胞类型特定靶点 神经元。目的2-体外电生理学、免疫组织化学、扩张显微镜和共聚焦显微镜的应用 确定抑制终末如何沿着特定的NA神经元表达，以及抑制如何形成强度 以NA进行编码。我的结果将为电路如何利用特殊的抑制性神经元进行感觉提供洞察力 以及抑制如何通过其对强度编码的影响来塑造谱时间加工。