Deconstructing complexity: serial block-face electron microscopic analysis of the hippocampal mossy fiber synapse
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The hippocampal mossy fiber (MF) terminal is among the largest and most complex synaptic structures in the brain. Our understanding of the development of this morphologically elaborate structure has been limited because of the inability of standard electron microscopy techniques to quickly and accurately reconstruct large volumes of neuropil. Here we use serial block-face electron microscopy (SBEM) to surmount these limitations and investigate the establishment of MF connectivity during mouse postnatal development. Based on volume reconstructions, we find that MF axons initially form bouton-like specializations directly onto dendritic shafts, that dendritic protrusions primarily arise independently of bouton contact sites, and that a dramatic increase in presynaptic and postsynaptic complexity follows the association of MF boutons with CA3 dendritic protrusions. We also identify a transient period of MF bouton filopodial exploration, followed by refinement of sites of synaptic connectivity. These observations enhance our understanding of the development of this highly specialized synapse and illustrate the power of SBEM to resolve details of developing microcircuits at a level not easily attainable with conventional approaches.
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The mossy fiber-CA3 PN synapse is accessible to quantitative structural analysis by electron microscopy, high-pressure freezing, and freeze-fracture replica labeling.
“Finally, it is accessible to quantitative structural analysis by EM [34,35], high-pressure freezing (HPF) [36–38], and freeze-fracture replica labeling (FRL) [39].”
From Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons (2024) · cites this paper as [35]
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- Authors
- Wilke, S. A., Antonios, J. K., Bushong, E. A., Badkoobehi, A., Malek, E., Hwang, M., Terada, M., Ellisman, M. H., & Ghosh, A.
- Affiliations
- University of California San Diego (US)
- F. Hoffmann-La Roche AG (CH)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-01-09
- Volume
- 33
- Issue
- 2
- Pages
- 507-522
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3756657
- OpenAlex
- W2143454033
- Cited by
- 179
- References
- 38
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 9 · 2023: 17 · 2022: 10 · 2021: 13 · 2020: 13 · 2019: 18 · 2018: 15 · 2017: 16 · 2016: 18 · 2015: 17 · 2014: 13 · 2013: 4
- FWCI
- 8.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NS064124)
- National Institute of General Medical Sciences (T32GM007198)
- National Institute of Neurological Disorders and Stroke (R01NS064124, NS064124)
- National Center for Research Resources (P41RR004050)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- mossy fiber synapses, hippocampus, CA3, synaptic development, postnatal development, boutons, dendritic protrusions, filopodia, synapse refinement, volume reconstruction, mice
- MeSH terms
- Animals, Animals, Newborn, Axons, Dendrites, Image Processing, Computer-Assisted, Mice, Inbred C57BL, Microscopy, Electron, Nerve Fibers, Pseudopodia, Quality Control, Software, Synapses, Presynaptic Terminals, Neuropil, Mossy Fibers, Hippocampal, Mice
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