Molecular and Physiological Diversity of MSO Neurons and the Influence of Auditory Experience

MSO 神经元的分子和生理多样性以及听觉体验的影响

• 批准号: 9612147
• 负责人: David B Haimes
• 金额: $ 3.87万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9612147
• 关键词: Acoustic Stimulation; Action Potentials; Address; Affect; Age; Antibodies; Auditory; Auditory system; Axon; Bilateral; Binaural; Brain; Brain Stem; Cell Nucleus; Cells; Closure by clamp; Code; Conductive hearing loss; Cues; Data; Development; Electrophysiology (science); Exhibits; Experimental Models; Fire - disasters; Frequencies; Generations; Hearing; Immunohistochemistry; Income; Individual; Ion Channel; Kinetics; Label; Language Development; Length; Literature; Location; Mammals; Measurement; Measures; Membrane; Modeling; Molecular; Morphology; Neurons; Noise; Operative Surgical Procedures; Pattern; Phase; Physiological; Population; Population Heterogeneity; Potassium Channel; Property; Sensorineural Hearing Loss; Signal Transduction; Sodium; Sodium Channel; Sound Localization; Stimulus; Synapses; Testing; Time; Training; United States; Weight Gain; Work; auditory stimulus; base; experience; experimental study; hearing impairment; medial superior olive; mindfulness; patch clamp; relating to nervous system; response; sound; stem; voltage

Project Summary The Medial Superior Olive (MSO) is a mammalian brainstem nucleus that computes cues used for azimuthal sound localization (interaural time differences, ITDs). Functionally, sound localization has been theorized to be a necessary component not just for the simple acquisition of spatial information, but also for higher order processing, such as language acquisition. 13% of people in the United States have some degree of hearing loss in both ears1, but we do not fully understand how these deficits impact the ability to perform basic computations, such as bilateral integration. Therefore, this work seeks to address specifically how models of hearing loss may impact neural diversity. Based on recent findings in our lab, the MSO contains a previously undescribed diverse population of repetitive firing neurons that are morphologically indistinguishable from phasic neuron counterparts, but respond to similar inputs. The membrane and response properties of these neurons are consistent with the time course of slower components of sounds, such as envelopes. This evidence suggests that the diversity of MSO response patterns may reflect the ability of the nucleus to encode a broader array of sound features than previously thought. Within this context, we question whether situations of hearing loss may restrict diversity of response properties, and thus irreparably effect the ability of mammals to respond to both fast and slow spatial cues. To test this hypothesize, we plan to use a combination of electrophysiology and immunohistochemistry to measure response patterns of MSO neurons in a conductive hearing loss model and a model of decorrelated information, lacking spatial cues. We predict that if repetitive firing neurons of the MSO are not present in the two experimental models, then normally patterned auditory stimuli are likely necessary for the development of these response types. Secondly, we hypothesize that the diversity of response types stems from a mechanistic alteration of spike generation in MSO neurons. We predict that in models of hearing loss, auditory features will no longer fine-tune the expression of voltage-gated sodium channels to generate a diverse set of responses. We will test this by using antibody labeling for specific subunits of sodium channels and pulling nucleated patches to isolate and measure somatic sodium currents. Together, these results will push our understanding of how hearing loss affects diverse populations of neurons, while adding to our much-needed understanding of how intrinsic neuron properties are shaped by auditory activity.

项目摘要 内侧橄榄（MSO）是一种哺乳动物的脑干核，计算用于用于 方位角声音定位（室内时间差，ITD）。在功能上，声音本地化已经 理论是为了简单地获取空间信息，而是用于 高阶处理，例如语言获取。美国有13％的人有一定程度 两种耳朵的听力损失1，但我们不完全了解这些缺陷如何影响执行能力 基本计算，例如双边整合。因此，这项工作旨在专门解决如何 听力损失的模型可能会影响神经多样性。 根据我们实验室的最新发现，MSO包含以前未描述的不同人群 重复的射击神经元在形态上与阶段性神经元同行无法区分，但 响应类似的输入。这些神经元的膜和反应特性与 较慢的声音组成部分（例如信封）的时间过程。这些证据表明 MSO响应模式可能反映了细胞核编码一系列声音特征的能力 以前想到。在这种情况下，我们质疑听力损失的情况是否可能限制 响应特性，因此不可挽回地影响哺乳动物对快速和缓慢的空间响应的能力 提示。为了测试这种假设，我们计划将电生理学和免疫组织化学的组合用于 测量导电听力损失模型中MSO神经元的响应模式和非相关模型 信息，缺乏空间提示。我们预测，如果MSO的重复发射神经元不存在 两种实验模型，然后通常需要形成的听觉刺激才能开发 这些响应类型。 其次，我们假设响应类型的多样性源于机械改变 MSO神经元中的峰值产生。我们预测，在听力损失的模型中，听觉功能将不再 微调电压门控钠通道的表达，以产生各种反应。我们将测试 通过对钠通道的特定亚基进行抗体标记和拉动核斑块以分离 并测量体钠电流。这些结果在一起将推动我们对听力损失的理解 影响神经元的不同种群，同时增加了我们急需的内在神经元的理解 属性是通过听觉活动来塑造的。