Morphological details contribute to neuronal response variability within the same cell type

Neuronal responses are inherently variable and similar characteristics can arise from multiple combinations of cellular parameters, with electrical diversity and variable branching patterns contributing to degeneracy. The contribution of morphological details, such as the diameter and length of dendritic branches, to response variability and degeneracy in neurons with a given branching pattern remains unclear. We address this question by using a model database approach with spatially extended, conductance-based compartmental models to study the variability of response features, such as resting membrane potential, input resistance, spike count, first spike latency, spike height, and spike width. Using 15 reconstructed morphologies of leech touch cells with fixed branching patterns, we identified thousands of parameter sets that were consistent with the experimentally measured response features in all the tested morphologies. Even when the electrical parameters were kept equal across reconstructed morphologies, variability in response features arose from the morphological details, beyond the well-known dependencies on the total membrane area and input resistance. Varying the spatial distribution of ion channels revealed that spike response features are influenced by the location of spike initiation zones with higher conductance density. Nevertheless, biologically plausible responses can arise from distinct locations of spike initiation zones, or even with a homogeneous distribution of ion channels. Furthermore, comparing the simulated spike responses from two morphological subtypes of leech touch cells revealed that the previously published systematic differences cannot be explained by the morphological differences alone. A larger total conductance of voltage-gated ion channels was required to reproduce the experimental finding of an increased spike count and a larger spike amplitude in the larger morphological subtype. In conclusion, morphological details interact with branching patterns, ion channel distribution and electrical properties, contributing significantly to the variability and degeneracy of neuronal responses.