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展需要这些输入的适当激活。除了对正常电路的发展发挥作用外，对双侧人工耳蜗患者的最新评估表明，他们新获得的双耳输入提供了一些改进的能力，可以在安静和噪音的情况下了解其本地化声音并理解语音。因此，尽管我们能够处理复杂的听觉刺激，例如只用一只耳朵来处理语音，但双耳提示提供了其他关键信息。不幸的是，对于这些双侧人工耳蜗患者中的某些人只是“一些”改进。我们仍处于婴儿期，知道如何通过助听器或耳蜗植入物最佳地向听力或聋哑人出现这种刺激。这条路径上的主要障碍之一是，我们仍然不完全了解与双耳处理有关的基本脑干电路以及该电路用于提取关键听觉提示的机制。内侧上橄榄（MSO）是脑干听觉核，也是听觉途径中的第一个双耳部位，其中两只耳朵激活了主要输入。到目前为止，它是人类上橄榄络合物中听觉脑干核中最突出的脑干核。有趣的是，几乎所有患有自闭症谱障碍（ASD）的儿童都具有听觉相关的功能障碍，而MSO是自闭症大脑中最严重，最稳定地畸形的脑干核。所有这些观察结果都表明，如果我们要设计适当的方法在受损条件下激活该核，对MSO结构和功能的了解至关重要。在使用类似于人类的听觉脑干的动物的实验中，这种努力受到了几种功能的阻碍，这些功能使MSO中的细胞很难获取和记录。我们拥有完美的方法，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细胞的解剖学和生理特征，这些特征在其双耳任务中至关重要。该方法涉及记录这些细胞对听觉刺激的响应，而不是从其细胞体中，而是从轴突远距离远距离与细胞核的远程刺激。在确定对一个或两只耳朵的听觉刺激的响应特征后，我们可以将移动染料（神经生物素）注入单个轴突中，该轴突填充了整个细胞体，树突状树和轴突侧支场。这使我们有机会在光和电子显微镜水平上也评估这些生理表征的细胞的重要解剖特征。我们真诚的信念是，这里提出的实验将提供关键信息，以提高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大脑和受损大脑的听力。