A Comparative Computer Simulation of Dendritic Morphology

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Abstract
Computational modeling of neuronal morphology is a powerful tool for understanding developmental processes and structure-function relationships. We present a multifaceted approach based on stochastic sampling of morphological measures from digital reconstructions of real cells. We examined how dendritic elongation, branching, and taper are controlled by three morphometric determinants: Branch Order, Radius, and Path Distance from the soma. Virtual dendrites were simulated starting from 3,715 neuronal trees reconstructed in 16 different laboratories, including morphological classes as diverse as spinal motoneurons and dentate granule cells. Several emergent morphometrics were used to compare real and virtual trees. Relating model parameters to Branch Order best constrained the number of terminations for most morphological classes, except pyramidal cell apical trees, which were better described by a dependence on Path Distance. In contrast, bifurcation asymmetry was best constrained by Radius for apical, but Path Distance for basal trees. All determinants showed similar performance in capturing total surface area, while surface area asymmetry was best determined by Path Distance. Grouping by other characteristics, such as size, asymmetry, arborizations, or animal species, showed smaller differences than observed between apical and basal, pointing to the biological importance of this separation. Hybrid models using combinations of the determinants confirmed these trends and allowed a detailed characterization of morphological relations. The differential findings between morphological groups suggest different underlying developmental mechanisms. By comparing the effects of several morphometric determinants on the simulation of different neuronal classes, this approach sheds light on possible growth mechanism variations responsible for the observed neuronal diversity. Neurons in the brain have a variety of complex arbor shapes that help determine both their interconnectivity and functional roles. Molecular biology is beginning to uncover important details on the development of these tree-like structures, but how and why vastly different shapes arise is still largely unknown. We developed a novel set of computer models of branching in which measurements of real nerve cell structures digitally traced from microscopic imaging are resampled to create virtual trees. The different rules that the models use to create the most similar virtual trees to the real data support specific hypotheses regarding development. Surprisingly, the arborizations that differed most in the optimal rules were found on opposite sides of the same type of neuron, namely apical and basal trees of pyramidal cells. The details of the rules suggest that pyramidal cell trees may respond in unique and complex ways to their external environment. By better understanding how these trees are formed in the brain, we can learn more about their normal function and why they are often malformed in neurological diseases.