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 听觉感官处理需要通过行动电位精确地进行神经元通信 微秒。神经系统通过专门提高固有膜特性和突触来实现这一精度 传播，特别是神经抑制。神经抑制通过提高选择性 神经元特别明显刺激和神经抑制的问题被认为是感觉问题的基础 耳鸣，超源和与年龄有关的听力损失（ARHL）。在鸟类听觉的脑干中，抑制实际上是 来自上级橄榄核（儿子）。儿子中的神经元从两个不同的平行线接收兴奋性输入 电路：同侧耳蜗核（NA），该核编码来自听觉神经的强度信息， 并从同侧重合检测层层核（NL）中，该核编码二进制时间的信息 耳蜗核核细胞（NM）。体外研究表明有2个电生理学 然而，在儿子中，表型，单个刺激性和补品射击反应，初步数据显示了第三个 表型，一种图案化的表型。增加声音强度在一部分中提高了相锁功能 laminaris神经元细胞核，表明SON中有可能从Na和NL收敛，但是它尚未 被证明了。重要的是，Burger等。 （2005年）证明了儿子神经元的同侧向na投射 NL和耳蜗核磁核或对比儿子。但是，尚不清楚这些表型是否 基于不同的项目。研究表明，抑制作用提高了NM的定时神经元的精度 和NL，但是对NA中的强度编码的影响（包含许多不同的细胞类型）尚不清楚。抑制性 终端在Na中异质表达，其中有些看似聚集在细胞体上，而另一些则在不同 树突。 NA中的电生理多样性已显示出沿多种操作模式存在。这是 不清楚抑制终端是否与NA的功能异质性有关，尤其是在速率编码神经元中 这些编码光谱信息的动态范围用于强度编码。该项目的目的是确定 儿子中的神经元如何适应良好的脑干电路以及它们如何影响强度编码神经元 遵循两个具体目标。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儿子中以及SON不同项目的细胞类型的特定目标 神经元。目标2-在体外电生理学，免疫组织化学，膨胀显微镜和共聚焦显微镜下使用 确定如何沿特定NA神经元表达抑制终端以及抑制作用如何形状强度 在NA中进行编码。我的结果将提供有关电路如何利用专门抑制性神经元进行感觉的见解 处理以及如何通过对强度编码的影响来塑造光谱处理。