Supralinear dendritic Ca2+ signalling in young developing CA1 pyramidal cells

Abstract

Although Ca2+ is critically important in activity-dependent neuronal development, not much is known about the regulation of dendritic Ca2+ signals in developing neurons. Here, we used ratiometric Ca2+ imaging to investigate dendritic Ca2+ signalling in rat hippocampal pyramidal cells during the first 1-4 weeks of postnatal development. We showthat active dendritic backpropagation of Nav channel-dependent action potentials (APs) evoked already large dendritic Ca2+ 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 Ca2+ load increased about four times during the first 4 weeks, the peak amplitude of free Ca2+ concentration was balanced by a four-fold increase in Ca2+ buffer capacity ks (~70 vs. ~280). Furthermore, Ca2+ 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 Ca2+ signals in young cells. Most importantly, during prolonged theta-burst stimulation dendritic Ca2+ 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 Ca2+ extrusion. As Ca2+ influx is four-fold smaller in young cells, the larger Ca2+ signals are generated using four times less ATPconsumption.Taken together, the data suggest that active backpropagations regulatedendritic Ca2+ signals during early postnatal development. Remarkably, during prolonged AP firing, Ca2+ signals are several times larger in young than in mature cells as a result of activity-dependent regulation of Ca2+ extrusion rates.