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.

项目概要 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来实现这种精度 传播，特别是神经抑制。神经抑制通过增加选择性来增强感觉处理 神经元对特别显着的刺激和神经抑制问题被认为是感觉问题的根源，例如 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，抑制作用实际上是由 完全来自上橄榄核（SON）。 SON 中的神经元从两个不同的并行接收兴奋性输入 电路：同侧耳蜗角核（NA），编码来自听神经的强度信息， 以及来自同侧重合检测核层状核 (NL)，该核对双耳计时信息进行编码 耳蜗大细胞核 (NM)。体外研究表明，有 2 种电生理机制 然而，初步数据揭示了 SON 中的第三种表型：单尖峰反应和强直放电反应。 表型，一种模式化的强直表型。增加声音强度可增强部分子集的锁相能力 层状核神经元，表明 SON 中的 NA 和 NL 可能会收敛，但实际上并没有 已被证明。重要的是，伯格等人。 (2005) 证明 SON 神经元要么同侧投射到 NA， NL，与耳蜗大细胞核，或对侧 SON。然而，尚不清楚这些表型是否 不同预测的背后。研究表明，抑制可以提高 NM 中神经元计时的精度 和 NL，但对包含许多不同细胞类型的 NA 中强度编码的影响尚不清楚。抑制性 NA 末端的表达呈异质性，一些看似聚集在细胞体上，另一些则聚集在远端 树突。 NA 中的电生理多样性已被证明存在于一系列操作模式中。这是 尚不清楚抑制性末端是否与 NA 中的功能异质性有关，特别是在速率编码神经元中 对光谱信息的动态范围进行编码以进行强度编码。该项目的目标是确定 SON 中的神经元如何适应特征明确的脑干回路，以及它们如何影响 SON 中的强度编码神经元 以下两个具体目标。目标 1 – 使用体外电生理学、突触刺激和神经元重建 确定如何将输入集成到 SON 中以及 SON 不同预测的细胞类型特定目标 神经元。目标 2- 使用体外电生理学、免疫组织化学、扩展显微镜和共焦显微镜 确定抑制末端如何沿着特定 NA 神经元表达以及抑制如何塑造强度 NA 中的编码。我的结果将深入了解电路如何利用专门的抑制神经元进行感觉 处理，以及抑制如何通过其对强度编码的影响来塑造光谱时间处理。