Synaptic Vesicle Dynamics at Excitatory Hippocampal Synapses

兴奋性海马突触的突触小泡动力学

• 批准号: 8320864
• 负责人: THOMAS SCHIKORSKI
• 金额: $ 29.06万
• 依托单位: UNIVERSIDAD CENTRAL DEL CARIBE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8320864
• 关键词: Advanced Development; Analgesics; Anticonvulsants; Calcium; Calcium Channel; Development; Electron Microscopy; Epilepsy; Foundations; Future; Goals; Grant; Hippocampus (Brain); Horseradish Peroxidase; Intervention; Knowledge; Laboratories; Lead; Learning; Levetiracetam; Ligands; Memory; Mental Depression; Modeling; Molecular; Morphology; Neuraxis; Neurons; Neurotransmitters; Outcome; Pain; Patients; Pattern; Pharmacologic Substance; Presynaptic Terminals; Recycling; Regulation; Reporter Genes; Role; Seizures; Signal Pathway; Synapses; Synaptic Vesicles; Synaptic plasticity; Technology; Testing; chronic pain; information processing; insight; neurotransmitter release; presynaptic; prevent; synaptic function; voltage

DESCRIPTION (provided by applicant): Synaptic vesicle dynamics govern the release of neurotransmitter and regulation of synaptic vesicle dynamics will control synaptic function and short-term plasticity. Here, we investigate the function of the a2d subunit of voltage sensitive calcium channels and propose that it is a powerful regulator of synaptic vesicle dynamics. Therefore, altering a2d subunit function via pharmaceutical intervention may slow synaptic vesicle dynamics and reduce neurotransmitter release and enhance short-term depression. a2d ligands are such pharmaceutical intervention and are potent analgesic and anticonvulsant drugs. Thus scrutinizing the function of the a2d subunit will lead to new insights about the regulation of synaptic vesicle dynamics. Furthermore, exploiting the signaling pathway downstream of the a2d subunit may lead to promising, future targets for the development of advanced anticonvulsant and analgesic drugs.

描述（由申请人提供）：突触小泡动力学控制神经递质的释放，突触小泡动力学的调节将控制突触功能和短期可塑性。在这里，我们研究了电压敏感钙通道 a2d 亚基的功能，并提出它是突触小泡动力学的强大调节剂。因此，通过药物干预改变 a2d 亚基功能可能会减缓突触小泡动力学，减少神经递质释放并增强短期抑郁。 a2d配体就是这样的药物干预，并且是有效的镇痛和抗惊厥药物。因此，仔细研究 a2d 亚基的功能将带来关于突触小泡动力学调节的新见解。此外，利用 a2d 亚基下游的信号通路可能会为先进抗惊厥和镇痛药物的开发带来有希望的未来目标。