Physiological and Behavioral Assessment of Lateral Efferent Function

描述（由申请人提供）：在I型听神经（AN）外周突起上的外侧橄榄耳蜗（OCV）传出末梢被策略性地放置，以提供AN活动的强大和动态调节。我们已经开发出了方法来损害的脑干，这使得我们的实验室和其他人显示听觉诱发电位（CAP，ABR）幅度的变化，可以特别归因于神经支配的损失。这使我们假设，听觉神经末梢作用于听觉神经外周过程，以增加AN纤维的动态范围，这反过来又具有改善强度辨别的功能。我们提出的具体目标测试这一假设，使用MPTP暂时中断耳蜗的听觉过程，而不中断传入或中央听觉通路。具体目标1使用电子显微镜、免疫细胞化学和全神经记录来检验以下假设：MPTP对神经元的破坏将（H1a）诱导纤维和终末的短暂神经元特异性损失，其损失将（H1b）导致AN自发活动、适应和动态范围的降低。(H1c)更大的形态破坏将与对AN响应的更多影响相关。具体目标2是基于初步结果，表明当共同传出包含DA和其他神经递质，免疫标记的MPTP应用程序后，两者都减少。这使我们假设（H2），当多巴胺和其他神经递质共同包含在同一纤维中时，它们可以被MPTP“共同破坏”，包括被认为是兴奋性的神经递质的破坏。具体目标3使用单个单位AN记录来测试以下假设：耳蜗的神经支配的破坏将（H3a）抑制自发AN活动，（H3b）改变AN的声音诱导反应，以及（H3c）减少AN的紧张性适应，导致高（H）比例的“重新分布”，中（M）和低（L）自发频率（SR）纤维具体目标4使用行为心理物理学来测试MPTP诱导的神经传出神经中断将（H4a）改变信号感知响度的动态范围和（H4b）降低强度的敏锐度的假设。相关的心理生理辨别任务。(H4c)MPTP对频率辨别力没有影响。这些研究将增加我们对耳蜗第一突触复合体的频率辨别作用机制的认识。他们将测试对响度感知和强度辨别的贡献。因此，将有临床相关性的干预措施，以保护AN免受兴奋性毒性损伤（噪音）和治疗“鸡尾酒会综合征”和类似的处理障碍，其中，在嘈杂的背景下，神经元可能在检测信号中发挥重要作用。

DESCRIPTION (provided by applicant): Lateral olivocochlear (LOG) efferent endings on Type I auditory nerve (AN) peripheral processes are strategically placed to provide a powerful and dynamic regulation of AN activity. We have developed methods to lesion the LOG which allowed our lab and others to show changes in auditory evoked potential (CAP, ABR) amplitudes that could specifically be attributed to the loss of LOG innervation. This has led us to hypothesize that the LOG acts on auditory nerve peripheral processes to increase dynamic range across AN fibers, which in turn has the function of improving intensity discrimination. Our proposed specific aims test this hypothesis using MPTP to transiently disrupt LOG processes in the cochlea, without disrupting afferents or the central auditory pathways. Specific Aim 1 uses electron microscopy, immunocytochemistry and whole nerve recording to test the hypothesis that LOG disruption by MPTP will (H1a) induce a transient LOG specific loss of fibers and terminals whose loss will (H1b) result in decreases in AN spontaneous activity, adaptation and dynamic range. (H1c) A greater morphological disruption will correlate with more effect on AN responses. Specific Aim 2 is based on preliminary results that show that when LOG efferents co-contain both DA and other neurotransmitters, immunolabeling for both decreases following MPTP application. This leads us to hypothesize (H2) that dopamine and other LOG transmitters can be "co-disrupted" by MPTP when they are co-contained in the same fiber, including disruption of neurotransmitters believed to be excitatory. Specific Aim 3 uses single unit AN recording to test the hypothesis that disruption of the LOG innervation of the cochlea will (H3a) suppress spontaneous AN activity, (H3b) alter sound-induced responses of AN, and (H3c) reduce tonic adaptation of AN, resulting in a "redistribution" of the proportion of High (H), Medium (M) and Low (L) spontaneous rate (SR) fibers Specific Aim 4 uses behavioral psychophysics to test the hypotheses that MPTP-induced disruption of LOG efferents will (H4a) alter dynamic range for perceived loudness of signals and (H4b) decrease acuity for intensity-related psychophysical discrimination tasks. (H4c) MPTP will have no effect on frequency discrimination These studies will increase our knowledge of mechanisms of LOG action at the first synaptic complex in the cochlea. They will test the LOG contribution to loudness perception and intensity discrimination. As such there will be clinical relevance towards interventions to protect AN from excitotoxic injury (from noise) and treatment of "cocktail party syndrome" and similar processing disorders, where the LOG may play an important role in detecting signals in a noisy background.