Physiological and Behavioral Assessment of Lateral Efferent Function

描述（由申请人提供）：I型听神经（AN）外周突上的侧耳蜗（LOG）传出末梢被战略性地放置，以提供a活动的强大和动态调节。我们已经开发出损伤LOG的方法，使我们的实验室和其他人能够显示听觉诱发电位（CAP， ABR）振幅的变化，这些变化可能具体归因于LOG神经支配的丧失。这使我们假设LOG作用于听神经外周过程，从而增加AN纤维的动态范围，从而具有提高强度辨别的功能。我们提出的具体目标是利用MPTP在不破坏传入或中央听觉通路的情况下，短暂地破坏耳蜗中的LOG过程来验证这一假设。Specific Aim 1使用电子显微镜、免疫细胞化学和全神经记录来验证假说，即MPTP破坏LOG将（H1a）诱导纤维和终端的短暂LOG特异性损失，其损失将（H1b）导致AN自发活性、适应性和动态范围的降低。（H1c）更大的形态破坏与对AN反应的更大影响相关。特异性目标2基于初步结果，该结果表明，当LOG传出神经同时含有DA和其他神经递质时，MPTP应用后两者的免疫标记都降低。这导致我们假设（H2）多巴胺和其他LOG递质可以被MPTP“共同破坏”，当它们共同包含在同一纤维中时，包括被认为是兴奋性的神经递质的破坏。Specific Aim 3使用单单元AN记录来验证耳蜗LOG神经支配的破坏会（H3a）抑制自发性AN活动，（H3b）改变AN的声诱导反应，（H3c）降低AN的张力适应，导致High的比例“重新分配”(H)。中(M)和低(L)自发率（SR）纤维特异性目标4使用行为心理物理学来验证mptp诱导的LOG传出信号中断将（H4a）改变感知信号响度的动态范围，（H4b）降低与强度相关的心理物理辨别任务的灵敏度。这些研究将增加我们对LOG在耳蜗第一突触复合体中的作用机制的认识。他们将测试LOG对响度感知和强度辨别的贡献。因此，对保护AN免受兴奋性毒性损伤（来自噪音）和治疗“鸡尾酒会综合症”和类似加工障碍的干预措施将具有临床意义，其中LOG可能在嘈杂背景下检测信号方面发挥重要作用。

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.