Physiological and Behavioral Assessment of Lateral Efferent Function

描述(申请人提供)：外侧橄榄耳(原木)传出末梢上的I型听神经(AN)周围突起是战略性的位置，以提供一个强大的和动态的活动调节。我们已经开发出损害LOG的方法，使我们的实验室和其他实验室能够显示听觉诱发电位(CAP，ABR)幅度的变化，这些变化可能具体归因于LOG神经支配的丧失。这导致我们假设，对数作用于听神经外周突起，以增加纤维的动态范围，进而具有改善强度辨别的功能。我们提出的具体目标是使用MPTP在不干扰传入神经或中枢听觉通路的情况下，瞬时扰乱耳蜗中的记录过程，以检验这一假说。具体目的1使用电子显微镜、免疫细胞化学和全神经记录来验证MPTP破坏对数的假说(H1a)会导致纤维和终末的一过性对数特异性丢失(H1b)会导致自发活动、适应性和动态范围的降低。(H1c)更大的形态破坏将与对AN反应的更多影响相关。具体目标2是基于初步结果，该结果表明，当原木传出同时含有DA和其他神经递质时，MPTP应用后两者的免疫标记都会减少。这导致我们假设(H2)，当多巴胺和其他对数递质被共同包含在同一纤维中时，它们可以被MPTP“共同干扰”，包括被认为是兴奋性的神经递质的破坏。特定目的3使用单个单位的AN记录来检验这样的假设，即破坏耳蜗对数神经支配将(H3a)抑制自发的AN活动，(H3b)改变AN的声诱导反应，(H3c)减少AN的紧张性适应，导致高(H)、中(M)和低(L)自发频率(SR)纤维的比例的“重新分配”。特定目的4使用行为心理物理学来检验假设，MPTP诱导的对数传出中断将(H4a)改变感知信号响度的动态范围和(H4b)降低强度相关心理物理任务的敏锐度。(H4c)MPTP对频率辨别没有影响，这些研究将增加我们对耳蜗第一突触复合体LOG作用机制的了解。他们将测试对数对响度感知和强度辨别的贡献。因此，对于防止兴奋性毒性损伤(噪声)的干预措施以及“鸡尾酒会综合症”和类似的加工障碍的治疗将具有临床意义，在这些情况下，测井可能在检测噪声背景中的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.