The stochastic nature of action potential backpropagation in apical tuft dendrites.

In cortical pyramidal neurons, backpropagating action potentials (bAPs) supply Ca to synaptic contacts on dendrites. To determine whether the efficacy of AP backpropagation into apical tuft dendrites is stable over time, we performed dendritic Ca and voltage imaging in rat brain slices. We found that the amplitude of bAP-Ca in apical tuft branches was unstable, given that it varied from trial to trial (termed "bAP-Ca flickering"). Small perturbations in dendritic physiology, such as spontaneous synaptic inputs, channel inactivation, or temperature-induced changes in channel kinetics, can cause bAP flickering. In the tuft branches, the density of Na and K channels was sufficient to support local initiation of fast spikelets by glutamate iontophoresis. We quantified the time delay between the somatic AP burst and the peak of dendritic Ca transient in the apical tuft, because this delay is important for induction of spike-timing dependent plasticity. Depending on the frequency of the somatic AP triplets, Ca signals peaked in the apical tuft 20-50 ms after the 1st AP in the soma. Interestingly, at low frequency (<20 Hz), the Ca peaked sooner than at high frequency, because only the 1st AP invaded tuft. Activation of dendritic voltage-gated Ca channels is sensitive to the duration of the dendritic voltage transient. In apical tuft branches, small changes in the duration of bAP voltage waveforms cause disproportionately large increases in dendritic Ca influx (bAP-Ca flickering). The stochastic nature of bAP-Ca adds a new perspective on the mechanisms by which pyramidal neurons combine inputs arriving at different cortical layers. The bAP-Ca signal amplitudes in some apical tuft branches randomly vary from moment to moment. In repetitive measurements, successful AP invasions are followed by complete failures. Passive spread of voltage from the apical trunk into the tuft occasionally reaches the threshold for local Na spike, resulting in stronger Ca influx. During a burst of three somatic APs, the peak of dendritic Ca in the apical tuft occurs with a delay of 20-50 ms depending on AP frequency.