Spikelets in Pyramidal Neurons: Action Potentials Initiated in the Axon Initial Segment That Do Not Activate the Soma
Fig 7
Mechanisms of spikelet generation in pyramidal neurons.
A: Sketch of the pyramidal-cell neuron model. The axon initial segment (AIS) can be divided in the proximal part (dark gray), where high-threshold NaV1.2 channels accumulate, and the distal part, where low-threshold NaV1.6 channels accumulate (dark green). High-threshold NaV1.2 channels are present at lower densities throughout the soma and dendrites (light gray). Low-threshold NaV1.6 channels are located throughout the axon (light green), but at lower densities than in the distal AIS (see Methods). We distinguish four different scenarios (AP, Sp1, Sp2, Sp3), which are described in detail in what follows. AP: Strong enough somato-dendritic inputs initiate an AP at the distal AIS (dark green). The AP then propagates down the axon and back to the soma and into the dendrites. Sp1: Weaker and briefer somato-dendritic inputs give rise to somatic spikelets if the AP initiated at the AIS fails to trigger a somatic AP. However, the axonal AP propagation to the postsynaptic targets remains unaffected. Sp2: Antidromic spikelets occur when an AP initiated in the distal axon propagates to the soma, but does not suffice to evoke a somatic AP. Sp3: In neurons with the axon connected to a basal dendrite, spikelets can also be evoked by inputs to the axon-carrying dendrite. These inputs can evoke an AP at the AIS without passing the soma first. The evoked AP, in turn, propagates down the axon but might fail to trigger a somato-dendritic spike, so a somatic spikelet appears. B: Mean somatic voltage threshold for the four scenarios illustrated in A: orthodromic APs (AP, N = 579), orthodromic spikelets (Sp1, N = 63), antidromic spikelets (Sp2, N = 194), and spikelets evoked by inputs to the axon-carrying dendrite (Sp3, N = 100). Error bars mark standard deviation. C: Mean somatic voltage slope in the 5-ms interval before the event, for the four scenarios illustrated in A.