Neural population activity determines the timing of synaptic inputs, which arrive to dendrites, cell bodies and axon initial segments (AISs) of cortical neurons. Action potential initiation in the AIS (AIS-APs) is driven by input integration, and the phase preference of AIS-APs during network oscillations is characteristic to cell classes. Distal regions of cortical axons do not receive synaptic inputs, yet experimental induction protocols can trigger retroaxonal action potentials (RA-APs) in axons distal from the soma. We report spontaneously occurring RA-APs in human and rodent cortical interneurons that appear uncorrelated to inputs and population activity. Network linked triggering of AIS-APs versus input independent timing of RA-APs of the same interneurons result in disparate temporal contribution of a single cell to in vivo network operation through perisomatic and distal axonal firing.

Human-specific cognitive abilities depend on information processing in the cerebral cortex, where neurons are significantly larger and sparser compared to rodents. We found that, in synaptically-connected layer 2/3 pyramidal cells (L2/3 PCs), soma-to-soma signal propagation delay is similar in humans and rodents. Thus, to compensate for the increase in neurons size, membrane potential changes must propagate faster in human axons and/or dendrites. Dual somato-dendritic and somato-axonal patch recordings show that action potentials (APs) propagation speed is similar in human and rat axons, but the forward propagation of the EPSPs and the back-propagating APs are ~1.7-fold faster in human dendrites. Faithful biophysical models of human and rat L2/3 PCs, combined with pharmacological manipulations of membrane properties, showed that the larger dendritic diameter, combined with differences in cable properties, underlie the accelerated signal propagation in human cortical circuits. The implication for information processing in the human brain are discussed.