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

项目摘要 内侧上级橄榄核（MSO）是哺乳动物脑干的一个核团，它计算用于 方位音定位（耳间时间差，ITD）。在功能上，声音定位已经被 理论上，它不仅是获取空间信息的必要组成部分， 高级处理，如语言习得。美国13%的人有一定程度的 双耳听力损失1，但我们并不完全了解这些缺陷如何影响执行能力 基本计算，如双边积分。因此，这项工作旨在具体解决如何 听力损失模型可能会影响神经多样性。 根据我们实验室最近的发现，MSO包含了一个以前未描述的多样化的种群， 重复放电神经元在形态上与相位神经元对应物无法区分，但 响应类似的输入。这些神经元的膜和反应特性与 声音的较慢分量的时间过程，例如包络。这些证据表明， MSO反应模式可能反映了细胞核编码更广泛的声音特征的能力， 以前认为。在这种情况下，我们质疑听力损失的情况是否会限制听力的多样性。 响应特性，从而不可挽回地影响哺乳动物对快速和慢速空间 线索为了验证这一假设，我们计划使用电生理学和免疫组织化学相结合的方法， 测量传导性听力损失模型和去相关模型中MSO神经元的响应模式 信息，缺乏空间线索。我们预测，如果MSO的重复放电神经元不存在于 两个实验模型，然后正常模式的听觉刺激可能是必要的发展， 这些反应类型。 第二，我们假设反应类型的多样性源于一种机械的改变， MSO神经元中尖峰的产生。我们预测，在听力损失模型中，听觉特征将不再 微调电压门控钠通道的表达，以产生多种反应。我们将测试 这是通过使用抗体标记钠通道的特定亚基， 测量体细胞钠电流总之，这些结果将推动我们了解听力损失是如何 影响不同的神经元群体，同时增加了我们对内在神经元如何 属性是由听觉活动塑造的。

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.