The stochastic nature of action potential backpropagation in apical tuft dendrites

In cortical pyramidal neurons, backpropagating action potentials (bAPs) supply Ca²⁺ to synaptic contacts on dendrites. To determine whether the efficacy of AP backpropagation into apical tuft dendrites is stable over time, we performed dendritic Ca²⁺ and voltage imaging in rat brain slices. We found that the amplitude of bAP-Ca²⁺ in apical tuft branches was unstable, given that it varied from trial to trial (termed "bAP-Ca²⁺ 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 Ca²⁺ 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, Ca²⁺ signals peaked in the apical tuft 20-50 ms after the 1st AP in the soma. Interestingly, at low frequency (<20 Hz), the Ca²⁺ peaked sooner than at high frequency, because only the 1st AP invaded tuft. Activation of dendritic voltage-gated Ca²⁺ 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 Ca²⁺ influx (bAP-Ca²⁺ flickering). The stochastic nature of bAP-Ca²⁺ adds a new perspective on the mechanisms by which pyramidal neurons combine inputs arriving at different cortical layers.NEW & NOTEWORTHY The bAP-Ca²⁺ 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 Ca²⁺ influx. During a burst of three somatic APs, the peak of dendritic Ca²⁺ in the apical tuft occurs with a delay of 20-50 ms depending on AP frequency.