Pohle Jörg, Bischofberger Josef
Department of Biomedicine, Physiological Institute, University of Basel, Basel, Switzerland Physiology of Neural Networks, Central Institute of Mental Health Mannheim, Mannheim, Germany.
Department of Biomedicine, Physiological Institute, University of Basel, Basel, Switzerland
J Physiol. 2014 Nov 15;592(22):4931-49. doi: 10.1113/jphysiol.2014.281931. Epub 2014 Sep 19.
Although Ca(2+) is critically important in activity-dependent neuronal development, not much is known about the regulation of dendritic Ca(2+) signals in developing neurons. Here, we used ratiometric Ca(2+) imaging to investigate dendritic Ca(2+) signalling in rat hippocampal pyramidal cells during the first 1-4 weeks of postnatal development. We show that active dendritic backpropagation of Nav channel-dependent action potentials (APs) evoked already large dendritic Ca(2+) transients in animals aged 1 week with amplitudes of ∼150 nm, similar to the amplitudes of ∼160 nM seen in animals aged 4 weeks. Although the AP-evoked dendritic Ca(2+) load increased about four times during the first 4 weeks, the peak amplitude of free Ca(2+) concentration was balanced by a four-fold increase in Ca(2+) buffer capacity κs (∼70 vs. ∼280). Furthermore, Ca(2+) extrusion rates increased with postnatal development, leading to a slower decay time course (∼0.2 s vs. ∼0.1 s) and more effective temporal summation of Ca(2+) signals in young cells. Most importantly, during prolonged theta-burst stimulation dendritic Ca(2+) signals were up to three times larger in cells at 1 week than at 4 weeks of age and much larger than predicted by linear summation, which is attributable to an activity-dependent slow-down of Ca(2+) extrusion. As Ca(2+) influx is four-fold smaller in young cells, the larger Ca(2+) signals are generated using four times less ATP consumption. Taken together, the data suggest that active backpropagations regulate dendritic Ca(2+) signals during early postnatal development. Remarkably, during prolonged AP firing, Ca(2+) signals are several times larger in young than in mature cells as a result of activity-dependent regulation of Ca(2+) extrusion rates.
尽管钙离子（Ca(2+)）在依赖活动的神经元发育中至关重要，但对于发育中神经元树突状钙离子信号的调节却知之甚少。在此，我们使用比率式钙离子成像技术，研究出生后第1至4周大鼠海马锥体细胞中的树突状钙离子信号传导。我们发现，在1周龄动物中，电压门控钠通道（Nav）依赖的动作电位（AP）的树突状主动回传已经引发了幅度约为150纳米的大型树突状钙离子瞬变，这与4周龄动物中观察到的约160纳摩尔的幅度相似。尽管在最初的4周内，动作电位诱发的树突状钙离子负荷增加了约四倍，但游离钙离子浓度的峰值幅度通过钙离子缓冲能力κs增加四倍（约70对约280）而得到平衡。此外，随着出生后发育，钙离子外排速率增加，导致年轻细胞中钙离子信号的衰减时间进程变慢（约0.2秒对约0.1秒），并且钙离子信号的时间总和更有效。最重要的是，在长时间的θ波爆发刺激期间，1周龄细胞中的树突状钙离子信号比4周龄细胞中的大两倍，并且远大于线性总和预测的值，这归因于活动依赖的钙离子外排减慢。由于年轻细胞中的钙离子内流小四倍，因此产生较大的钙离子信号时ATP消耗减少四倍。综上所述，数据表明主动回传在出生后早期发育期间调节树突状钙离子信号。值得注意的是，在长时间动作电位发放期间，由于活动依赖的钙离子外排速率调节，年轻细胞中的钙离子信号比成熟细胞中的大几倍。
