In Vivo Analysis of Synaptic Function in Zebrafish

斑马鱼突触功能的体内分析

• 批准号: 7054959
• 负责人: Hua Wen
• 金额: $ 5.04万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7054959
• 关键词: acetylcholine; alternatives to animals in research; biological signal transduction; calcium flux; cholinergic receptors; genetically modified animals; homeostasis; membrane proteins; motor neurons; neural transmission; neuromuscular junction; neuronal transport; postdoctoral investigator; receptor expression; striated muscles; synaptic vesicles; voltage /patch clamp; zebrafish

DESCRIPTION (provided by applicant): Recent evidence suggests that altered postsynaptic activity induces homeostatic regulation of presynaptic transmitter release at vertebrate neuromuscular junction. The long-term goal of this study is to understand the in vivo mechanisms underlying the homeostatic regulation. A zebrafish preparation is developed in the lab wherein the spinal motor neuron and its target muscle cell can be simultaneously patch clamped in intact animal. Using this technique, synaptic transmission at the wild type neuromuscular junction will be first characterized. Secondly, the hypothesis that presynaptic release is regulated by postsynaptic activity will be tested following manipulations that alter the functional postsynaptic acetylcholine receptor density. Thirdly, available mutant fish lines with aberrant calcium signaling will be used to test for a role of calcium release from internal stores in initiating the retrograde signaling that leads to presynaptic compensation. Results from this study will contribute to our understanding of how synaptic transmission is maintained within a physiological range while allowing for activity-dependent modification, and understanding in etiology of related neural diseases.

描述（由申请人提供）：最近的证据表明，突触后活动的改变会诱导脊椎动物神经肌肉接头处突触前递质释放的稳态调节。这项研究的长期目标是了解稳态调节的体内机制。实验室开发了一种斑马鱼制剂，其中脊髓运动神经元及其目标肌肉细胞可以同时在完整动物中进行膜片钳。使用这种技术，将首先表征野生型神经肌肉接头处的突触传递。其次，突触前释放受突触后活动调节的假设将在改变功能性突触后乙酰胆碱受体密度的操作后进行测试。第三，具有异常钙信号传导的现有突变鱼系将用于测试内部储存的钙释放在启动导致突触前补偿的逆行信号传导中的作用。这项研究的结果将有助于我们了解突触传递如何维持在生理范围内，同时允许活动依赖性修饰，并了解相关神经疾病的病因学。