title: Supralinear dendritic Ca(2+) signalling in young developing CA1 pyramidal cells.
abstract: 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.
authors.affiliation: Department of Biomedicine, Physiological Institute, University of Basel, Basel, Switzerland Physiology of Neural Networks, Central Institute of Mental Health Mannheim, Mannheim, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Pohle
authors.affiliation: Department of Biomedicine, Physiological Institute, University of Basel, Basel, Switzerland Josef.Bischofberger@unibas.ch.
authors.forename: Josef
authors.initials: J
authors.lastname: Bischofberger
mesh_terms: D000200:Action Potentials; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D020013:Calcium Signaling; D003712:Dendrites / Q000378:metabolism* / Q000502:physiology; D017966:Pyramidal Cells / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013826:Theta Rhythm