Extracellular ATP is a widespread cell-to-cell signaling molecule in the brain, where it functions as a neuromodulator by activating glia and neurons. Although ATP exerts multiple effects on synaptic plasticity and neuro-glia interactions, as well as in mood disorders, the source and regulation of ATP release remain to be elaborated. Here, we define Calhm2 as an ATP-releasing channel protein based on in vitro and in vivo models. Conventional knockout and conditional astrocyte knockout of Calhm2 both lead to significantly reduced ATP concentrations, loss of hippocampal spine number, neural dysfunction and depression-like behaviors in mice, which can be significantly rescued by ATP replenishment. Our findings identify Calhm2 as a critical ATP-releasing channel that modulates neural activity and as a potential risk factor of depression.

中文翻译：

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Calhm2控制着抑郁样行为的发展过程中星形细胞ATP的释放。

细胞外ATP是大脑中一种广泛的细胞间信号分子，在其中它通过激活神经胶质细胞和神经元而充当神经调节剂。尽管ATP对突触可塑性和神经胶质细胞相互作用以及情绪障碍具有多种作用，但ATP释放的来源和调控仍有待阐明。在这里，我们根据体外和体内模型将Calhm2定义为ATP释放通道蛋白。Calhm2的常规敲除和条件性星形胶质细胞敲除均会导致ATP浓度显着降低，小鼠海马脊柱数量减少，神经功能障碍和抑郁样行为，这可以通过ATP补充得到明显缓解。我们的发现确定Calhm2是调节神经活动的重要ATP释放通道，并且是抑郁的潜在危险因素。