Dendritome Mapping Unveils Spatial Organization of Striatal D1/D2-Neuron Morphology

Area of Science:

• Neuroscience
• Computational Biology
• Systems Biology

Background:

• Neuronal morphology is crucial for brain function, but large-scale profiling is challenging.
• Understanding dendritic morphology of medium spiny neurons (MSNs) is key to deciphering striatal circuitry.
• Existing methods lack scalability for brain-wide morphological analysis of genetically defined neurons.

Purpose of the Study:

• To establish a generalizable pipeline for large-scale, brain-wide dendritic morphology profiling of genetically defined single neurons.
• To characterize and map the dendritic morphology of striatal D1- and D2-MSNs in the mouse brain.
• To investigate the impact of aging and Huntington's disease (HD) on MSN morphology.

Main Methods:

• Developed a computational pipeline for 3D reconstruction and reference-atlas mapping of single neurons.
• Generated a dataset of 3,762 reconstructed striatal D1- and D2-MSNs.
• Employed integrative morphometric analyses and a novel "eigen-morph" approach for regional feature summarization and clustering.

Main Results:

• Identified distinct dendritic morphologies of D1- and D2-MSNs influenced by anatomical location.
• Discovered 6 striatal modules with characteristic dendritic features and distinct corticostriatal inputs.
• Demonstrated that aging causes significant dendritic defects, while HD mice show selective length-related deficits in MSNs.

Conclusions:

• The study presents a systems-biology approach for profiling neuronal morphology at scale.
• Defined novel morphological territories for striatal D1/D2-MSNs.
• Revealed specific dendritic pathologies associated with aging and Huntington's disease in MSNs.