Abstract:
The co-existence and co-transmission of neuropeptides and small molecule neurotransmitters in the same neuron is a fundamental aspect of almost all neurons across various species. However, the differences regarding their in vivo spatiotemporal dynamics and underlying molecular regulation remain poorly understood. Here, we developed a GPCR-activation-based (GRAB) sensor for detecting short neuropeptide F (sNPF) with high sensitivity and spatiotemporal resolution. Furthermore, we explore the differences of in vivo dynamics and molecular regulation between sNPF and acetylcholine (ACh) from the same neurons. Interestingly, the release of sNPF and ACh shows different spatiotemporal dynamics. Notably, we found that distinct synaptotagmins (Syt) are involved in these two processes, as Syt7 and Sytα for sNPF release, while Syt1 for ACh release. Thus, this new GRAB sensor provides a powerful tool for studying neuropeptide release and providing new insights into the distinct release dynamics and molecular regulation between neuropeptides and small molecule neurotransmitters.
摘要:
神经肽和小分子神经递质在同一神经元中的共存和共同传递是各种物种中几乎所有神经元的基本方面。然而,关于它们体内时空动力学和潜在分子调控的差异仍然知之甚少。这里,我们开发了一种基于GPCR激活(GRAB)的传感器,用于检测短神经肽F(sNPF),具有高灵敏度和时空分辨率。此外,我们探讨了sNPF和来自同一神经元的乙酰胆碱(ACh)在体内动力学和分子调控上的差异。有趣的是,sNPF和ACh的释放表现出不同的时空动态。值得注意的是,我们发现这两个过程涉及不同的突触组分(Syt),作为sNPF发布的Syt7和Sytα,而Syt1为ACh释放。因此,这种新的GRAB传感器为研究神经肽释放提供了一个强大的工具,并为神经肽和小分子神经递质之间独特的释放动力学和分子调节提供了新的见解。