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bioRxiv · 10.1101/2025.09.15.676219

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

Sandbote, K.·Arkhypchuk, I.·Kretzberg, J.
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Abstract

A large body of literature offers an explanation on how electrical diversity and variable branching patterns of neurons contribute to degeneracy, enabling multiple solutions for a characteristic neuronal response. For neurons with the same branching pattern it is yet unclear, how finer morphological details, such as diameter and length of dendritic branches, contribute to response variability. We address this question using a model database approach with spatially extended, conductance-based compartmental models to study 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 several thousands of parameter sets that reproduced 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. This could not be explained by well-known dependencies on the total membrane area and input resistance. Systematically 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 different locations of spike initiation zones and even 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 a larger morphological subtype. In conclusion, electrical properties, morphological details, and ion channel distribution across the membrane all interact in their contribution to the functionality and response variability of neurons of the same cell type.

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Sandbote, K., Arkhypchuk, I., Kretzberg, J.. 2025-09-16. Morphological details contribute to neuronal response variability within the same cell type. https://doi.org/10.1101/2025.09.15.676219

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