Differential dendritic Ca2+ signalling in young and mature hippocampal granule cells

摘要

Neuronal activity is critically important for development and plasticity of dendrites, axons and synaptic connections. Although Ca²⁺ is an important signal molecule for these processes, not much is known about the regulation of the dendritic Ca²⁺ concentration in developing neurons. Here we used confocal Ca²⁺ imaging to investigate dendritic Ca²⁺ signalling in young and mature hippocampal granule cells, identified by the expression of the immature neuronal marker polysialated neural cell adhesion molecule (PSA-NCAM). Using the Ca²⁺-sensitive fluorescent dye OGB-5N, we found that both young and mature granule cells showed large action-potential evoked dendritic Ca²⁺ transients with similar amplitude of ∼200 nm, indicating active backpropagation of action potentials. However, the decay of the dendritic Ca²⁺ concentration back to baseline values was substantially different with a decay time constant of 550 ms in young versus 130 ms in mature cells, leading to a more efficient temporal summation of Ca²⁺ signals during theta-frequency stimulation in the young neurons. Comparison of the peak Ca²⁺ concentration and the decay measured with different Ca²⁺ indicators (OGB-5N, OGB-1) in the two populations of neurons revealed that the young cells had an ∼3 times smaller endogenous Ca²⁺-binding ratio (∼75 versus∼220) and an ∼10 times slower Ca²⁺ extrusion rate (∼170 s⁻¹versus∼1800 s⁻¹). These data suggest that the large dendritic Ca²⁺ signals due to low buffer capacity and slow extrusion rates in young granule cells may contribute to the activity-dependent growth and plasticity of dendrites and new synaptic connections. This will finally support differentiation and integration of young neurons into the hippocampal network.