(A) Reconstructed morphologies for four pyramidal neurons (PyCs) from mouse V1. (B) Biophysically detailed, ion-conductance models were fit for each cell constrained by its slice electrophysiology features and reconstructed morphology. Panels show model response vs. experimental data for one case (cell #2 in panel A). The panel shows the model performance in terms of f-I-response, spike waveform similarity and example subthreshold, suprathreshold somatic voltage traces (black) vs. the actual experimental traces (blue). (C) Average z-scored training errors for the four models (cell #1–4) for a set of electrophysiology parameters. (D) Left: schematic for different ChC configurations (green: dendritic excitation; colors along axon initial segment [AIS]: ChC inhibition innervation). Three inhibitory innervation patterns are considered that affect the temporal aspect of ChC synapse activation. Right: intracellular voltage response at soma when only excitation is active (green) vs. when AIS inhibition is co-active (red). (E) Increasing excitatory synaptic drive vs. PyC spike rate for the different inhibition scenarios (colors) for 9 vs. 15 total ChC synapses along the AIS. Results from one cell model (cell #2 in panel A) for different innervation realizations (line: mean; shaded area: SD). (F) Average PyC firing rate across the four single-cell models at fixed excitation across ChC configurations for increasing number of ChC synapses (bar: mean; error bar: SD; significance testing: Wilcoxon signed-rank test at 5% false discovery rate). (G) Effect of AIS vs. somatic inhibition barrages on PyC spike output (black: excitatory input barrage; red: inhibitory AIS barrage; left-to-right: difference between centroids is −100, –50, 0, 50, and 100 ms, respectively). Raster plots: spike output for AIS (top) vs. somatic (bottom) inhibitory barrage (all other properties remain identical). When the two barrages are coincident, AIS inhibition results in a decrease in PyC spiking vs. somatic inhibition. Data shown for multiple realizations in one model (cell #2 in panel A). (H, top) PyC spike output count for inhibition at the AIS vs. at the soma across four models and multiple realizations. (Bottom) The differential effect in inhibition as computed by the difference between soma and AIS spike counts divided by the sum of the spike counts. The ratio ranges between –1 and 1, where 1 represents inhibition at the AIS being 100% more effective than at the soma and 0 meaning no differential effect. The most prominent difference between AIS and somatic inhibition is for concurrent barrages when the number of ChC synapses along the AIS is between 4 and 15. Significance testing: Wilcoxon signed-rank test at 5% false discovery rate.