Increased neural activities reduced pH at the synaptic cleft and interstitial spaces. Recent studies have shown that protons function as a neurotransmitter. However, it remains unclear whether protons signal through a metabotropic receptor to regulate synaptic function. Here, we showed that GPR68, a proton-sensitive GPCR, exhibited wide expression in the hippocampus, with higher expression observed in CA3 pyramidal neurons and dentate granule cells. In organotypic hippocampal slice neurons, ectopically expressed GPR68-GFP was present in dendrites, dendritic spines, and axons. Recordings in hippocampal slices isolated from GPR68−/− mice showed a reduced fiber volley at the Schaffer collateral-CA1 synapses, a reduced long-term potentiation (LTP), but unaltered paired-pulse ratio. In a step-through passive avoidance test, GPR68−/− mice exhibited reduced avoidance to the dark chamber. These findings showed that GPR68 contributes to hippocampal LTP and aversive fear memory.

中文翻译：

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GPR68删除损害海马长期增强和被动回避行为。

神经活动的增加降低了突触间隙和间隙的pH。最近的研究表明，质子起神经递质的作用。然而，尚不清楚质子是否通过代谢型受体发出信号来调节突触功能。在这里，我们表明质子敏感的GPCR GPR68在海马中表现出广泛的表达，在CA3锥体神经元和齿状颗粒细胞中观察到更高的表达。在器官型海马切片神经元中，在树突，树突棘和轴突中存在异位表达的GPR68-GFP。从GPR68-/-小鼠分离的海马切片中的记录显示，在Schaffer侧支CA1突触处纤维齐射减少，长期增强（LTP）降低，但成对脉冲比率未改变。在逐步被动回避测试中，GPR68-/-小鼠对暗室的回避减少。这些发现表明，GPR68有助于海马LTP和厌恶恐惧记忆。