Communication between glia cells and neurons is crucial for brain functions, but the molecular mechanisms and functional consequences of gliotransmission remain enigmatic. Here we report that astrocytes express synaptobrevin II and cellubrevin as functionally non-overlapping vesicular SNARE proteins on glutamatergic vesicles and neuropeptide Y-containing large dense-core vesicles, respectively. Using individual null-mutants for Vamp2 (synaptobrevin II) and Vamp3 (cellubrevin), as well as the corresponding compound null-mutant for genes encoding both v-SNARE proteins, we delineate previously unrecognized individual v-SNARE dependencies of astrocytic release processes and their functional impact on neuronal signaling. Specifically, we show that astroglial cellubrevin-dependent neuropeptide Y secretion diminishes synaptic signaling, while synaptobrevin II-dependent glutamate release from astrocytes enhances synaptic signaling. Our experiments thereby uncover the molecular mechanisms of two distinct v-SNARE-dependent astrocytic release pathways that oppositely control synaptic strength at presynaptic sites, elucidating new avenues of communication between astrocytes and neurons.

中文翻译：

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星形胶质细胞通过两种不同的v-SNARE依赖性释放途径控制突触强度。

胶质细胞和神经元之间的交流对于大脑功能至关重要，但是神经胶质传输的分子机制和功能后果仍然难以捉摸。在这里我们报告星形胶质细胞表达synaptobrevin II和cellubrevin作为功能上不重叠的谷氨酸能囊泡和神经肽Y包含大密集核心囊泡上的囊性SNARE蛋白。使用针对Vamp2（突触纤维蛋白II）和Vamp3（cellubrevin）的单个无效突变体，以及用于编码两种v-SNARE蛋白质的基因的相应化合物无效突变体，我们描述了先前无法识别的星形细胞释放过程及其相关的单个v-SNARE依赖性对神经元信号传导的功能影响。具体来说，我们显示星形胶质细胞尿素依赖性神经肽Y分泌减少了突触信号传导，星形胶质细胞释放突触纤维蛋白II依赖的谷氨酸盐可增强突触信号传导。因此，我们的实验揭示了两个不同的v-SNARE依赖性星形胶质细胞释放途径的分子机制，这些途径相反地控制突触前位点的突触强度，从而阐明了星形胶质细胞和神经元之间交流的新途径。