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

项目摘要 内侧上橄榄核(MSO)是哺乳动物的脑干核团，它计算用于 方位声定位(耳间时间差，ITDS)。在功能上，声音本地化已经被 理论上被认为不仅是简单获取空间信息的必要组成部分，而且还 更高层次的处理，如语言习得。13%的美国人有不同程度的 双耳都有听力损失，但我们并不完全了解这些缺陷是如何影响执行能力的 基本计算，如双边积分。因此，这项工作寻求具体解决如何 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包含了以前没有描述过的多样化的种群 在形态上与相对应神经元无法区分的重复放电神经元，但 对类似的输入做出反应。这些神经元的膜和反应特性与 声音中较慢分量的时间进程，如信封。这一证据表明，生物多样性 MSO反应模式可能反映了核团编码更广泛的声音特征阵列的能力 之前的想法是。在这种背景下，我们质疑听力损失的情况是否会限制 反应特性，从而不可挽回地影响哺乳动物对快空间和慢空间的反应能力 暗示。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的组合来 在传导性听力损失模型和去相关模型中测量MSO神经元的反应模式 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 这些响应类型。 其次，我们假设，反应类型的多样性源于 MSO神经元中的棘波产生。我们预测，在听力损失的模型中，听觉特征将不再 微调电压门控钠通道的表达，以产生一系列不同的反应。我们将测试 这是通过使用钠通道特定亚单位的抗体标记和拉动有核斑块来分离 并测量体细胞钠电流。总而言之，这些结果将推动我们理解听力损失是如何 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 属性由听觉活动决定。

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.