RT Journal Article SR Electronic T1 Analysis of synapse-level neuronal morphology in human post-mortem brain tissue JF bioRxiv FD Cold Spring Harbor Laboratory SP 558817 DO 10.1101/558817 A1 Sujan C. Das A1 Danli Chen A1 W. Brandon Callor A1 Eric Christensen A1 Hilary Coon A1 Megan E. Williams YR 2019 UL http://biorxiv.org/content/early/2019/02/22/558817.abstract AB Many cognitive and psychiatric disorders are thought to be disorders of the synapse, yet the precise synapse defects underlying these disorders remain unknown. Because synapses are highly specialized anatomical structures, defects in synapse formation and function can often be observed as changes in micro-scale neuroanatomy. Unfortunately, few methods are available for accurate analysis of synapses in human post-mortem tissues. Here, we present a new methodological pipeline for assessing synapse-level neuron morphology in human post-mortem tissue that is accurate, rapid, and relatively inexpensive. Our method uses small tissue blocks from postmortem human brains, immersion fixation, single cell resolution by dye labeling, and confocal microscopy. As proof of principle, we analyzed pre-and postsynaptic structures from hippocampi of 13 individuals aged 4 months to 71 years. Our results suggest that postsynaptic CA1 dendritic spine shape and density are stable across ages, while presynaptic DG mossy fiber boutons undergo significant structural rearrangements with normal aging. This suggests that mossy fiber synapses, which play a major role in learning and memory, remain dynamic throughout life. Importantly, we find no effect of postmortem intervals up to 28 hours on neuron morphology. Thus, the ease of our new protocol should facilitate higher powered studies of human synapse structure in healthy and diseased states.