A single-synapse resolution survey of PSD95-positive synapses in twenty human brain regions

Mapping the molecular composition of individual excitatory synapses across the mouse brain reveals high synapse diversity with each brain region showing a distinct composition of synapse types. As a first step towards systematic mapping of synapse diversity across the human brain, we have labelled and imaged synapses expressing the excitatory synapse protein PSD95 in twenty human brain regions, including 13 neocortical, two subcortical, one hippocampal, one cerebellar and three brainstem regions, in four phenotypically normal individuals. We quantified the number, size and intensity of individual synaptic puncta and compared their regional distributions. We found that each region showed a distinct signature of synaptic puncta parameters. Comparison of brain regions showed that cortical and hippocampal structures are similar, and distinct from those of cerebellum and brainstem. Comparison of synapse parameters from human and mouse brain revealed conservation of parameters, hierarchical organization of brain regions and network architecture. This work illustrates the feasibility of generating a systematic single-synapse resolution atlas of the human brain, a potentially significant resource in studies of brain health and disease.

Automated summary

Mapping of individual excitatory synapses across the mouse brain has shown high synapse diversity, with each brain region displaying a distinct composition of synapse types. This study on human brain regions labeled and imaged synapses expressing the excitatory synapse protein PSD95, revealing unique synaptic puncta parameters in different regions. Comparison between human and mouse brain synapse parameters demonstrate conservation, hierarchical organization of brain regions, and distinct network architecture.