TY - JOUR
T1 - A single‐synapse resolution survey of PSD95‐positive synapses in twenty human brain regions
AU - Curran, Olimpia E.
AU - Qiu, Zhen
AU - Smith, Colin
AU - Grant, Seth G. N.
N1 - Copyright:
© 2020 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
KW - automated image analysis
KW - human post-mortem brain tissue
KW - postsynaptic density protein 95
KW - regional diversity
KW - synaptome atlas
KW - synaptome mapping
UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85087319345&origin=inward
U2 - 10.1111/ejn.14846
DO - 10.1111/ejn.14846
M3 - Article
SN - 0953-816X
VL - 54
SP - 6864
EP - 6881
JO - European Journal of Neuroscience
JF - European Journal of Neuroscience
IS - 8
ER -