The ability of presynaptic dopamine terminals to tune neurotransmitter release to meet the demands of neuronal activity is critical to neurotransmission. Although vesicle content has been assumed to be static, in vitro data increasingly suggest that cell activity modulates vesicle content. Here, we use a coordinated genetic, pharmacological, and imaging approach in Drosophila to study the presynaptic machinery responsible for these vesicular processes in vivo. We show that cell depolarization increases synaptic vesicle dopamine content prior to release via vesicular hyperacidification. This depolarization-induced hyperacidification is mediated by the vesicular glutamate transporter (VGLUT). Remarkably, both depolarization-induced dopamine vesicle hyperacidification and its dependence on VGLUT2 are seen in ventral midbrain dopamine neurons in the mouse. Together, these data suggest that in response to depolarization, dopamine vesicles utilize a cascade of vesicular transporters to dynamically increase the vesicular pH gradient, thereby increasing dopamine vesicle content.

中文翻译：

---

神经元去极化通过VGLUT驱动增加的多巴胺突触囊泡负荷。

突触前多巴胺末端调节神经递质释放以满足神经元活动需求的能力对于神经传递至关重要。尽管已经假定囊泡含量是静态的，但体外数据越来越多地表明细胞活性调节囊泡含量。在这里，我们在果蝇中使用协调的遗传，药理和成像方法来研究负责体内这些水泡过程的突触前机制。我们表明细胞去极化增加通过水泡超酸化释放之前的突触囊泡多巴胺含量。这种去极化诱导的过度酸化是由囊泡谷氨酸转运蛋白（VGLUT）介导的。值得注意的是 在小鼠腹侧中脑多巴胺神经元中均观察到了去极化诱导的多巴胺囊泡过度酸化及其对VGLUT2的依赖性。总之，这些数据表明，响应去极化，多巴胺囊泡利用级联的囊泡转运蛋白动态地增加了囊泡的pH梯度，从而增加了多巴胺囊泡的含量。