A framework for comparative analysis of human and mouse cortical neuron dendrites in corresponding brain regions

Cross-species comparisons of neuronal morphology can reveal evolutionary diversification of cortical organization, but they remain limited by scarce human reconstructions, uncertain regional correspondence and scale-dependent morphometrics. Here we introduce a region correspondence framework to compare single-neuron dendritic morphology between mouse and human cortex. Corresponding cortical regions were rigorously defined by integrating anatomical annotations, functional evidence and registration stability and then evaluated using cross-species transcriptomic cell composition profiles. We analyzed dendritic reconstructions of 2,363 human and 16,011 mouse neurons from frontal, parietal and temporal lobes, comparing size-normalized local morphometric features within matched regions. Human cortical neurons showed higher branching frequency and shorter branching intervals, indicating compact local dendritic architecture beyond proportional size enlargement. Local morphology also showed stronger lobe-level separability in humans, associated mainly with spatial dendritic organization, whereas mouse separability reflected branching topology. Additional molecular, physiological, metabolic and geometric analyses showed partial concordance with morphology-based lobe separability, supporting divergent organization of cortical dendrites across species.