Dendritome mapping reveals the spatial organization of striatal neuron morphology

Dendritic arbors are essential for neuronal computation and signal propagation, yet large-scale single-neuron morphology studies remain challenging. Here we present a systems biology approach, termed 'dendritome mapping', to profile the dendritic morphology of genetically defined single neurons in mice, unveiling striatal medium spiny neuron (MSN) morphological territories and aging-associated or disease-associated alterations. We generated 3,762 three-dimensional-reconstructed and reference-atlas-mapped striatal D1-type and D2-type MSNs, revealing distinct impacts of D1/D2 genotypes and striatal locations on MSN morphology. To analyze dendritic variation at a finer resolution than known anatomical landmarks permit, we assigned MSNs to latticed cubic boxes within the reference brain atlas, summarized a morphometric representation ('eigen-morph') for each box and clustered boxes with shared morphometry. This identified six modules with characteristic dendritic features and spanning contiguous striatal territories, each receiving distinct corticostriatal inputs. Finally, we found that aging confers dendritic atrophy in both D1-MSNs and D2-MSNs, whereas Huntington's disease mice exhibit MSN-type and regional-specific defects.