Structure and function of the medial superior olive

描述（由申请人提供）：双耳听力在语言和语言感知的发展中起着关键作用，因为大脑双耳电路的正常发育需要这些输入的适当激活。除了有助于正常电路的发展之外，最近对双侧人工耳蜗患者的评估表明，他们新获得的双耳输入可以改善他们在安静和有噪音的情况下定位声音和理解语言的能力。因此，尽管我们只用一只耳朵就能处理复杂的听觉刺激，比如说话，但双耳线索提供了额外的关键信息。不幸的是，这只是“一些”改善这些双侧人工耳蜗患者。对于如何通过助听器或人工耳蜗将这种刺激最佳地呈现给听障人士或聋人，我们还处于初级阶段。在这条道路上的主要障碍之一是，我们仍然没有完全了解涉及双耳处理的基本脑干电路以及该电路用于提取关键听觉线索的机制。内侧上橄榄核（MSO）是脑干听觉核，是听觉通路中第一个双耳部位，双耳激活的主要输入在此汇聚。到目前为止，它是人类上橄榄核复合体中最突出的听觉脑干核。有趣的是，几乎所有患有自闭症谱系障碍（ASD）的儿童都有听觉相关的功能障碍，而MSO是自闭症大脑中最严重和持续畸形的脑干核。所有这些观察结果表明，如果我们要设计在受损条件下激活该核的适当方法，则更彻底地了解MSO的结构和功能是至关重要的。利用与人类相似的听觉脑干的动物进行实验的这些努力受到了几个特征的阻碍，这些特征使得从MSO细胞中获取和记录极其困难。我们已经完善了绕过细胞核这些不利特征的方法，使我们能够明确地评估MSO细胞的解剖和生理特征，这些特征对它们的双耳任务至关重要。该方法包括记录这些细胞对听觉刺激的反应，而不是从它们的细胞体，而是从远离细胞核的轴突。在确定了单耳或双耳对听觉刺激的反应特征后，我们可以将一种可移动的染料（神经生物素）注射到单个轴突中，该染料填充整个细胞体、树突树和轴突侧枝野。这使我们有机会在光镜和电镜水平上评估这些生理特征细胞的重要解剖特征。我们真诚地相信，这里提出的实验将提供重要的信息，这将有助于我们了解正常大脑的听力机制，以及如何更好地促进老年和受损大脑的听力。

DESCRIPTION (provided by applicant): Binaural hearing plays a key role in the development of speech and language perception because the normal development of the brain's binaural circuitry requires the proper activation of these inputs. Besides being instrumental in the development of normal circuitry, recent evaluations of bilateral cochlear implant patients indicates that their newly acquired binaural inputs provide some improvements in their abilities to localize sound and to understand speech in quiet and in the presence of noise. Thus, although we are able to process complex auditory stimuli like speech with only one ear, binaural cues provide additional critical information. Unfortunately it is only "some" improvement for some of these bilateral cochlear implant patients. We are still in the infancy stages of knowing how to optimally present such stimuli to the hard of hearing or deaf via hearing aids or cochlear implants. One of the major impediments on this path is that we still do not have a complete understanding the basic brainstem circuitry involved in binaural processing and the mechanisms used by this circuitry to extract the critical auditory cues. The medial superior olive (MSO) is a brainstem auditory nucleus and the first binaural site in the auditory pathway where major inputs activated by the two ears converge. It is by far the most prominent of the auditory brainstem nuclei in the human superior olivary complex. Interestingly, virtually all children with autistic spectral disorder (ASD) have auditory related dysfunction and the MSO is the most severely and consistently malformed brainstem nucleus in the autistic brain. All of these observations would indicate that a more thorough understanding of MSO structure and function is critical if we are to design appropriate methods of activating this nucleus under compromised conditions. Such efforts in experiments using animals with auditory brainstems similar to humans have been hampered by several features that make it extremely difficult to access and record from cells in the MSO. We have perfected methods that bypass these unfavorable features of the nucleus and will allow us to unequivocally evaluate the anatomical and physiological features of MSO cells that are vital in their binaural mission. The method involves recording the responses of these cells to auditory stimulation not from their cell bodies but remotely from their axons at some distance from the nucleus. After determining the response features to auditory stimuli presented to one or both ears we can inject a mobile dye (Neurobiotin) into the individual axon which fills the entire cell body, dendritic tree and axon collateral field. This gives us the opportunity to evaluate the important anatomical features of these physiologically characterized cells at the light and electron microscopic level as well. It is our sincere belief that the experiments proposed here will provide critical information that will advance our understanding of hearing mechanisms in the normal brain and how to better facilitate hearing in the aged and damaged brain.