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Analysis of synapse-level neuronal morphology in human post-mortem brain tissue

Sujan C. Das, Danli Chen, W. Brandon Callor, Eric Christensen, Hilary Coon, Megan E. Williams
doi: https://doi.org/10.1101/558817
Sujan C. Das
1Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT84112, USA
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Danli Chen
1Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT84112, USA
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W. Brandon Callor
3Utah State Office of Medical Examiner, Utah Department of Health, Salt Lake City, UT, USA
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Eric Christensen
3Utah State Office of Medical Examiner, Utah Department of Health, Salt Lake City, UT, USA
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Hilary Coon
1Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT84112, USA
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  • For correspondence: megan.williams@neuro.utah.edu hilary.coon@hsc.utah.edu
Megan E. Williams
2Department of Neurobiology and Anatomy, University of Utah School of Medicine, UT84112, USA
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  • For correspondence: megan.williams@neuro.utah.edu hilary.coon@hsc.utah.edu
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ABSTRACT

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.

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Posted February 22, 2019.
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Analysis of synapse-level neuronal morphology in human post-mortem brain tissue
Sujan C. Das, Danli Chen, W. Brandon Callor, Eric Christensen, Hilary Coon, Megan E. Williams
bioRxiv 558817; doi: https://doi.org/10.1101/558817
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Analysis of synapse-level neuronal morphology in human post-mortem brain tissue
Sujan C. Das, Danli Chen, W. Brandon Callor, Eric Christensen, Hilary Coon, Megan E. Williams
bioRxiv 558817; doi: https://doi.org/10.1101/558817

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