Structure and function of the medial superior olive

描述（由申请人提供）：双耳听力在言语和语言感知的发展中起着关键作用，因为大脑双耳回路的正常发展需要这些输入的适当激活。除了有助于正常电路的发展，最近对双侧人工耳蜗植入患者的评估表明，他们新获得的双耳输入提供了一些改善，他们的能力，以本地化的声音和理解语音在安静和噪音的存在。因此，虽然我们能够处理复杂的听觉刺激，如语音只有一只耳朵，双耳线索提供额外的关键信息。不幸的是，对于一些双侧人工耳蜗植入患者来说，这只是“一些”改善。我们仍然处于婴儿阶段，知道如何通过助听器或人工耳蜗植入物最佳地将这些刺激呈现给听力困难或失聪的人。在这条道路上的主要障碍之一是，我们仍然没有一个完整的理解基本的脑干回路参与双耳处理和该电路使用的机制，以提取关键的听觉线索。内侧上级橄榄（MSO）是脑干听觉核团，也是双耳听觉通路中的第一个双耳部位，双耳激活的主要输入在此会聚。它是人类上级橄榄复合体中最突出的听觉脑干核团。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团。所有这些观察结果都表明，如果我们要设计在妥协条件下激活该细胞核的适当方法，那么对MSO结构和功能的更透彻理解至关重要。在使用具有与人类相似的听觉脑干的动物进行的实验中，这种努力受到了几个特征的阻碍，这些特征使得MSO中的细胞非常难以访问和记录。我们已经完善的方法，绕过这些不利的特点，核，并将使我们能够明确评估的解剖和生理特征的MSO细胞是至关重要的，在他们的双耳使命。该方法涉及记录这些细胞对听觉刺激的反应，而不是来自细胞体，而是来自离核一定距离的轴突。在确定对呈现给一只或两只耳朵的听觉刺激的反应特征之后，我们可以将移动的染料（Neurobiotin）注射到单个轴突中，其填充整个细胞体、树突树和轴突侧支野。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关键信息，促进我们对正常大脑中听力机制的理解，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.