Synaptic Vesicle Dynamics at Excitatory Hippocampal Synapses

描述（由申请人提供）：突触囊泡动力学控制神经递质的释放，突触囊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性钙通道a2d亚基的功能，并提出它是突触囊泡动力学的一个强有力的调节器。因此，通过药物干预改变a2d亚基功能可能会减缓突触囊泡动力学，减少神经递质释放，增强短期抑郁。A2D配体是这样的药物干预，并且是有效的镇痛和抗惊厥药物。因此，仔细研究a2d亚基的功能将导致对突触囊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开发高级抗惊厥和镇痛药物带来有前途的未来目标。 公共卫生相关性：突触连接的功效控制中枢神经系统内的神经元活动。在癫痫或慢性疼痛患者中，神经元活动达到病理性高水平，并且突触功效的细微降低可以防止癫痫发作并减轻疼痛。在这个应用程序中，我们仔细检查是否可以利用限制含有突触囊泡的神经递质的可用性来降低突触功效。

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. PUBLIC HEALTH RELEVANCE: The efficacy of synaptic connections governs neuronal activity within the central nervous system. In patients with epilepsy or chronic pain neuronal activity reaches pathological high levels and a subtle reduction of synaptic efficacy may prevent seizures and alleviate pain. In this application, we scrutinize whether limiting the availability of neurotransmitter containing synaptic vesicles can be exploited to reduce synaptic efficacy.