Brain function relies on vesicular release of neurotransmitters at chemical synapses. The release probability depends on action potential‐evoked presynaptic Ca²⁺ entry, but also on the resting Ca²⁺ level. Whether these basic aspects of presynaptic calcium homeostasis show any consistent trend along the axonal path, and how they are controlled by local network activity, remains poorly understood. Here, we take advantage of the recently advanced FLIM‐based method to monitor presynaptic Ca²⁺ with nanomolar sensitivity. We find that, in cortical pyramidal neurons, action potential‐evoked calcium entry (range 10–300 nM), but not the resting Ca²⁺ level (range 10–100 nM), tends to increase with higher order of axonal branches. Blocking astroglial glutamate uptake reduces evoked Ca²⁺ entry but has little effect on resting Ca²⁺ whereas both appear boosted by the constitutive activation of group 1/2 metabotropic glutamate receptors. We find no consistent effect of transient somatic depolarization or hyperpolarization on presynaptic Ca²⁺ entry or its basal level. The results unveil some key aspects of presynaptic machinery in cortical circuits, shedding light on basic principles of synaptic connectivity in the brain.

中文翻译：

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荧光寿命成像揭示了谷氨酸摄取和 mGluR 对突触前 Ca2+ 的调节，而不是皮质神经元中的体细胞电压。

脑功能依赖于化学突触处神经递质的囊泡释放。释放概率取决于动作电位诱发的突触前 Ca ²⁺进入，但也取决于静息 Ca ²⁺水平。突触前钙稳态的这些基本方面是否显示出沿轴突路径的任何一致趋势，以及它们如何受本地网络活动控制，仍然知之甚少。在这里，我们利用最近先进的基于 FLIM 的方法来监测具有纳摩尔级灵敏度的突触前 Ca ^{2+ 。}我们发现，在皮质锥体神经元中，动作电位诱发的钙进入（范围 10-300 nM），而不是静息的 Ca ²⁺水平（范围 10-100 nM），随着轴突分支的高阶趋于增加。阻断星形胶质细胞谷氨酸摄取可减少诱发的 Ca ^{2+进入，但对静息 Ca 2+}几乎没有影响，而两者似乎都因 1/2 组代谢型谷氨酸受体的组成性激活而增强。我们发现瞬时体细胞去极化或超极化对突触前Ca ²⁺进入或其基础水平没有一致的影响。结果揭示了皮质回路中突触前机制的一些关键方面，揭示了大脑中突触连接的基本原理。