3D morphology-based clustering and simulation of human pyramidal cell dendritic spines

The dendritic spines of pyramidal neurons are the targets of most excitatory synapses in the cerebral cortex. They have a wide variety of morphologies, and their morphology appears to be critical from the functional point of view. To further characterize dendritic spine geometry, we used in this paper over 7,000 individually 3D reconstructed dendritic spines from human cortical pyramidal neurons to group dendritic spines using model-based clustering. This approach uncovered six separate groups of human dendritic spines. To better understand the differences between these groups, the discriminative characteristics of each group were identified as a set of rules. Model-based clustering was also useful for simulating accurate 3D virtual representations of spines that matched the morphological definitions of each cluster. This mathematical approach could provide a useful tool for theoretical predictions on the functional features of human pyramidal neurons based on the morphology of dendritic spines.Author summary: Dendritic spines of pyramidal neurons are the targets of most excitatory synapses in the cerebral cortex and their morphology appears to be critical from the functional point of view. Thus, characterizing this morphology is necessary to link structural and functional spine data and thus interpret and make them more meaningful. We have used a large database of more than 7,000 individually 3D reconstructed dendritic spines from human cortical pyramidal neurons that is first transformed into a set of 54 quantitative features characterizing spine geometry mathematically. The resulting data set is grouped into spine clusters based on a probabilistic model with Gaussian finite mixtures. We uncover six groups of spines whose discriminative characteristics are identified with machine learning methods as a set of rules. The clustering model allows us to simulate accurate spines from human pyramidal neurons to suggest new hypotheses of the functional organization of these cells.