Physiological and Behavioral Assessment of Lateral Efferent Function

外侧传出功能的生理和行为评估

• 批准号: 7850236
• 负责人: RICHARD A ALTSCHULER
• 金额: $ 17.05万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7850236
• 关键词: Acoustic Nerve; Acoustics; Action Potentials; Auditory Evoked Potentials; Auditory Perception; Auditory system; Behavior assessment; Behavioral; Cavia; Central Auditory Processing Disorder; Chronic; Cochlea; Complex; Detection; Development; Discrimination; Disease; Dopamine; Electron Microscopy; Enzymes; Fiber; Frequencies; Functional disorder; Future; Infusion procedures; Injury; Inner Hair Cells; Intervention; Knowledge; Lateral; Lesion; Loudness; Loudness Perception; MPTP Poisoning; Masks; Measures; Methods; Metric; Nerve; Nerve Fibers; Neurons; Neurotoxins; Neurotransmitters; Noise; Parvalbumins; Perception; Peripheral; Physiological; Play; Population; Presynaptic Terminals; Process; Psychophysics; Psychophysiology; Recovery; Regulation; Research Personnel; Role; Signal Transduction; Sound Localization; Specificity; Speech Sound; Synapses; Synaptophysin; System; Testing; Time; Tinnitus; Training; Transmission Electron Microscopy; auditory pathway; base; chromophore; clinically relevant; cocktail party syndrome; ear infection; immunocytochemistry; improved; improved functioning; lateral superior olive; middle ear; nerve supply; programs; research study; response; sound

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.

描述（由申请人提供）：I型听觉神经（AN）外围过程的侧面橄榄石（log）传出结尾是战略性的，以提供对活动的强大而动态的调节。我们已经开发了病变的方法，使我们的实验室和其他人能够显示出诱发的潜力（CAP，ABR）幅度的变化，这些幅度可能特别归因于日志神经的丧失。这使我们假设该日志作用于听觉神经外围过程，以增加纤维上的动态范围，从而又具有改善强度歧视的功能。我们提出的特定目的是使用MPTP检验该假设，以瞬时破坏耳蜗中的日志过程，而不会破坏传入者或中央听觉途径。特定目标1使用电子显微镜，免疫细胞化学和整个神经记录来测试以下假设：MPTP对数的破坏将（H1A）诱导损失损失（H1B）的瞬时对数特异性损失（H1B）导致自发活性，适应和动态范围的降低。 （H1C）更大的形态破坏将与对反应的影响更大。具体目标2基于初步结果，该结果表明，当对数产物共同包含DA和其他神经递质时，MPTP应用后两种降低的免疫标记。这使我们假设（H2）在同一纤维中共同插入时，多巴胺和其他对数发射器可以被MPTP“共同中断”，包括据信兴奋性的神经递质的破坏。特定目标3使用单个单元录制录制来测试以下假说：耳蜗的对数的破坏将（H3a）抑制自发的活动，（H3b）改变了AN的响应的声音诱导的响应，（H3C）（H3C）减少了An的张力适应，导致AN的张力适应，导致“高度（Med）（M中）（SR）（SR），Med（Med）（M中（S）） AIM 4使用行为心理物理学来测试MPTP引起的对数屈服的破坏将改变动态范围的假设，以改变动态范围，以了解信号的响度，而（H4B）降低了与强度相关的心理物理歧视任务的敏锐度。 （H4C）MPTP对频率歧视没有影响，这些研究将增加我们对耳蜗中第一个突触复合物的对数动作机制的了解。他们将测试对响度感知和强度歧视的对数贡献。因此，将对干预措施有临床意义，以保护抗激毒性损伤（免受噪声）和“鸡尾酒综合征”的处理和类似的处理障碍，在该障碍中，日志可能在嘈杂的背景下检测信号中起重要作用。