Postnatal development of dendritic calcium signaling in rat hippocampal pyramidal cells

In CA1 pyramidal neurons, dendritic calcium transients in stratum radiatum were evoked in
acute slices via backpropagating action potentials using patch clamp recordings.
Although calcium is critically important for activity-dependent neuronal development, not
much is known about the regulation of the dendritic calcium signals in developing neurons.
Here we used ratiometric calcium imaging to investigate dendritic calcium signalling in rat
hippocampal pyramidal cells during the first 1 to 4 weeks of postnatal development, focussing
on a comparison of 1 week vs 4 weeks old rats. We show for the first time that active
dendritic backpropagation of Nav-channel dependent action potentials evoked already large
dendritic calcium transients in one-week-old animals with amplitudes of ~140 nM similar to
mature pyramidal cells (~160 nM). Although, AP-evoked dendritic calcium load increases ~4
times during the first 4 weeks (~10 uM versus ~40 uM), this seems to be out-balanced by a
~3.5-times increase in calcium buffer capacity (~70 versus ~240). Furthermore, linear
summation of calcium transients in young and mature cells during brief bursts of APs was
similar. Surprisingly, repetitive theta-burst stimulation for two seconds showed ~2.5-times
larger dendritic calcium signals in 1 week-old rats than predicted by linear summation and
was about ~2-3-times larger than measured in 4 weeks old rats. We could show that this non-
linear summation of calcium transients was due to an activity-dependent slow-down of
calcium extrusion in the young neurons.
Taken together, the data suggest that active backpropagation regulate dendritic calcium
signals already during early postnatal development. Remarkably, calcium signals in young
neurons are even several times larger than in mature cells due to activity dependent regulation
of calcium extrusion rates. Extrusion rates are slower in young neurons compared to mature
neurons, 4.5-times for single APs and up to 8-times at the end of theta-burst stimulation.