Structure and function of the medial superior olive

内侧上橄榄的结构和功能

• 批准号: 8902103
• 负责人: PHILIP H SMITH
• 金额: $ 28.98万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8902103
• 关键词: Acoustic Stimulation; Action Potentials; Animals; Auditory; Axon; Belief; Bilateral; Brain; Brain Injuries; Brain Stem; Bypass; Cell Extracts; Cell Nucleus; Cells; Characteristics; Child; Cochlear Implants; Complex; Contralateral; Cues; Dendrites; Development; Devices; Disease; Dorsal; Dyes; Ear; Electrons; Environment; Evaluation; Event; Frequencies; Functional disorder; Goals; Health; Hearing; Hearing Aids; Hearing Impaired Persons; Human; Individual; Inferior Colliculus; Ipsilateral; Label; Lateral lemniscus; Length; Light; Link; Location; Mammals; Maps; Methods; Microscopic; Mission; Modeling; Morphology; Nature; Neurons; Noise; Nuclear; Pathway interactions; Patients; Pattern; Phase; Physiological; Play; Process; Property; Site; Sound Localization; Speech; Speech Perception; Staging; Stimulus; Structure; Synapses; System; Techniques; Time; Trees; aged; auditory nuclei; auditory pathway; auditory stimulus; binaural hearing; cell type; design; in vivo; infancy; language perception; lateral superior olive; medial superior olive; neurobiotin; neuronal cell body; research study; response; sound; sound frequency

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.

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，因为大脑双耳电路的正常发育需要这些输入的正确激活。除了有助于正常电路的发育之外，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可以提高他们在安静和有噪音的情况下定位声音和理解语音的能力。因此，尽管我们能够仅用一只耳朵处理复杂的听觉刺激（例如语音），但双耳线索提供了额外的关键信息。不幸的是，对于其中一些双侧人工耳蜗植入患者来说，这只是“一些”改善。我们仍处于了解如何通过助听器或人工耳蜗以最佳方式向听力困难或聋人呈现此类刺激的婴儿阶段。这条道路上的主要障碍之一是我们仍然没有完全理解双耳处理中涉及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，也是听觉通路中的第一个双耳部位，两耳激活的主要输入在此汇聚。它是迄今为止人类上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) 的儿童都有与听觉相关的功能障碍，而 MSO 是自闭症大脑中最严重且持续畸形的脑干核。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，对 MSO 结构和功能的更彻底了解至关重要。使用具有与人类相似的听觉脑干的动物进行的实验受到多种特征的阻碍，这些特征使得从 MSO 的细胞中访问和记录变得极其困难。我们拥有完善的方法，可以绕过细胞核的这些不利特征，并使我们能够明确评估 MSO 细胞的解剖和生理特征，这些特征对于其双耳任务至关重要。该方法涉及记录这些细胞对听觉刺激的反应，这些反应不是来自细胞体，而是来自距细胞核一定距离的轴突。在确定对一只或两只耳朵的听觉刺激的反应特征后，我们可以将一种移动染料（神经生物素）注射到填充整个细胞体、树突树和轴突侧支区域的单个轴突中。这使我们有机会在光和电子显微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听力机制以及如何更好地促进衰老和受损大脑听力的理解。