Preserving Axo - somatic Spiking Features Despite Diverse Dendritic 2 Morphology

20 Throughout the nervous system, cells belonging to a certain electrical class (e-class) sharing high similarity in 21 firing response properties may nevertheless have widely variable dendritic morphologies. To quantify the 22 effect of this morphological variability on the firing of layer 5 thick-tufted pyramidal cells (TTCs), a detailed 23 conductance-based model (CBM) was constructed for a 3D reconstructed exemplar TTC. The model exhibited 24 spike initiation in the axon and reproduced the characteristic features of individual spikes as well as of the 25 firing properties at the soma as recorded in a population of TTCs in young Wistar rats. When using these model 26 parameters over the population of 28 3D reconstructed TTCs, both axonal and somatic ion channel densities 27 had to be scaled linearly with the conductance load imposed on each of these compartments (ρaxon and ρ, 28 respectively). Otherwise, the firing of model cells deviated, sometimes very significantly, from the 29 experimental variability of the TTC e-class. The study provides experimentally testable predictions regarding 30 the co-regulation of axo-somatic membrane ion channels density for cells with different dendritic conductance 31 load, together with a simple and systematic method for generating reliable CBMs for the whole population of 32 modeled neurons belonging to a particular e-class with variable morphology as found experimentally. 33