Fig 5. Validation of results in a model cell with anatomically reconstructed morphology.

This model was previously fitted to account for BAC firing by Hay and colleagues [23]. Using their original parameters, we replicated the all-or-none modulation of bAPs by proximal inhibition (B), the compartmental modulation of bAPs versus calcium spikes in the morphologically complex dendrite (E-G), and the required time scales for proximal versus distal inhibition (C,E). Ionic conductances in the model by Hay et al. differed from those used in our simplified pyramidal cell model. We found the recovery of the bAP to be independent of the exact ion channel composition of the dendrite, as long as the interplay of sodium and counteracting currents allowed for an active propagation of the sodium spike. A: Morphology of the neuron. Somatic current injection as in [23] was used to elicit a bAP. Sites of proximal inhibition (blue) and oblique recording (yellow) are indicated. B: All-or-none modulation of the bAP along the apical dendrite, from the soma into the very distal apical tuft. C: Timing and strength of proximal inhibition (x- and y-axis, respectively) and its effect on the bAP amplitude in the oblique dendrite. Color-code as in Fig 3B/C. D: Somatic current injection paired with dendritic stimulation as in [23] was used to trigger BAC firing. Sites of proximal inhibition (blue), distal inhibition and recording (red), and apical tuft (pink) and oblique (yellow) recording are indicated and correspond to colored voltage traces in E to G. E: Distal inhibition inhibited BAC firing, but did not inhibit the bAP in the oblique dendrite. Inhibition of the calcium spike could be achieved for a range of timings (inset, same axes and color code as in B). F: Proximal inhibition inhibited the bAP in the oblique dendrite and BAC firing, if timed appropriately (inset). G: Without inhibition, pairing of bAP and distal input results in BAC firing [23].