Cross-species comparative analysis of single presynapses

Comparing brain structure across species and regions enables key functional insights. Leveraging publicly available data from a novel mass cytometry-based method, synaptometry by time of flight (SynTOF), we applied an unsupervised machine learning approach to conduct a comparative study of presynapse molecular abundance across three species and three brain regions. We used neural networks and their attractive properties to model complex relationships among high dimensional data to develop a unified, unsupervised framework for comparing the profile of more than 4.5 million single presynapses among normal human, macaque, and mouse samples. An extensive validation showed the feasibility of performing cross-species comparison using SynTOF profiling. Integrative analysis of the abundance of 20 presynaptic proteins revealed near-complete separation between primates and mice involving synaptic pruning, cellular energy, lipid metabolism, and neurotransmission. In addition, our analysis revealed a strong overlap between the presynaptic composition of human and macaque in the cerebral cortex and neostriatum. Our unique approach illuminates species- and region-specific variation in presynapse molecular composition.

Automated summary

Comparing brain structure across species and regions allows for important functional insights. In this study, a novel mass cytometry-based method called synaptometry by time of flight (SynTOF) was used to compare presynapse molecular abundance across three species and three brain regions. The results showed significant differences in presynaptic composition between human, macaque, and mouse samples, with a notable overlap between human and macaque in certain brain regions.