Synaptic Transmission During Neuronal Differentiation

神经元分化过程中的突触传递

基本信息

批准号：
7924218
负责人：
Kenna D Peusner
金额：
$ 63.35万
依托单位：
GEORGE WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-03 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7924218
关键词：
AMPA Receptors Adult Animal Model Animals Axon Behavior Behavioral Birds Birth Brain Cell Nucleus Cells Chickens Child Clinical Clinical Management Controlled Study Data Deafferentation procedure Development Drug usage Equilibrium Event Eye Movements Fiber Financial compensation Frequencies Ganglionectomy Glutamate Receptor Glutamates Goals Grant Head Human Injection of therapeutic agent Intervention Kinetics Labyrinth Learning Lesion Location Modeling Molecular Nature Neuronal Differentiation Neurons Pathology Patients Pattern Peripheral Play Positioning Attribute Posture Potassium Channel Process Quality of life Recovery Reflex control Regulation Rehabilitation therapy Research Rest Role Side Site Slice Sodium Channel Source Staging Stimulus Study Subject Symptoms Synapses Synaptic Transmission Syndrome Tissues Vestibular Nerve Vestibular nucleus structure Work behavior test biocytin computerized data processing density effective therapy equilibration disorder extracellular gamma-Aminobutyric Acid improved indium arsenide neuronal cell body patch clamp postsynaptic presynaptic receptor research study response vestibular reflex voltage

项目摘要

DESCRIPTION (provided by applicant): Unilateral peripheral vestibular lesions result in deficits in eye movements, posture, and balance, but the static symptoms usually diminish rapidly due to the process of vestibular compensation. Vestibular nuclei neurons must be intact for recovery, suggesting that adaptation involves these neurons. In fact, recovery of spontaneous spike firing in vestibular nuclei neurons bilaterally is a critical step for vestibular compensation to proceed. Our broad, long-term goal is to identify key cellular and molecular events orchestrating changes in vestibular nuclei neuron activity at early stages after lesions. Since a significant proportion of patients remain uncompensated, controls, compensated, and uncompensated subjects are studied. Experiments are focused on a distinct class of vestibular nuclei neurons, the principal cells of the tangential nucleus, from an established animal model, the chicken. Like humans, most chickens respond to unilateral vestibular ganglionectomy by compensating rapidly, but others remain uncompensated. We will study two critical stages: one day after the lesion when all the animals are uncompensated, and three days, when the majority of animals have compensated. We hypothesize that changes in the intact primary vestibular inputs and/or non-vestibular inputs dominate each stage of recovery. The specific aims include whole-cell patch-clamp recordings of frequency and kinetics of excitatory and inhibitory spontaneous synaptic events, and postsynaptic responses on vestibular-nerve and non-vestibular-nerve stimulation. We will determine the location and density of voltage-dependent sodium channels and AMPA receptor subunit expression in recorded PCs. The exact nature of non-vestibular terminals in the tangential nucleus will be determined using biocytin extracellular injections, combined with glutamate and GABA immunolabeling, and potassium channel immunolabeling of the terminals after lesions. Lesions in the labyrinths impair the quality of life and survival of the patient. Using drug interventions immediately after the onset of the vestibular syndrome could vastly improve patient rehabilitation. As we learn more about the pathology induced by vestibular deafferentation at the level of vestibular nuclei neurons, effective therapies can be targeted selectively to improve the clinical management of patients with balance disorders.

描述（由申请人提供）：单侧外围前庭病变会导致眼睛运动，姿势和平衡的缺陷，但是由于前庭补偿过程，静态症状通常会迅速减少。前庭核神经元必须完好无损以恢复，这表明适应涉及这些神经元。实际上，双侧的前庭核神经元中自发尖峰发射是前庭补偿的关键步骤。我们广泛的长期目标是确定关键的细胞和分子事件，这些事件在病变后的早期阶段策划了前庭核神经元活性的变化。由于很大一部分的患者仍未补偿，因此研究了对照，补偿和未补偿的受试者。实验集中于从已建立的动物模型鸡的一类不同的前庭核元，切向核的主要细胞。像人类一样，大多数鸡会通过迅速补偿而对单侧前庭神经节切除术反应，但其他鸡仍然没有补偿。我们将研究两个关键阶段：病变后的一天，所有动物都没有补偿，三天，大多数动物得到了补偿。我们假设完整的主要前庭输入和/或非vesibular输入的变化占据了恢复的每个阶段。具体目的包括频率的全细胞斑块钳记录以及兴奋性和抑制性自发突触事件的动力学，以及对前庭障碍和非卵巢刺激的突触后反应。我们将在记录的PC中确定电压依赖性钠通道和AMPA受体亚基表达的位置和密度。切向细胞核中非视域末端的确切性质将使用生物细胞外细胞外注射，与谷氨酸和GABA免疫标记，以及病后末端的钾通道免疫标记。迷宫中的病变会损害患者的生活质量和生存质量。前庭综合征开始后立即使用药物干预措施可以大大改善患者康复。随着我们更多地了解前庭核核神经元水平上的病理学诱导的病理，可以选择性地靶向有效的疗法，以改善平衡障碍患者的临床管理。