Three-Dimensional Structure and Composition of CA3→CA1 Axons in Rat Hippocampal Slices: Implications for Presynaptic Connectivity and Compartmentalization
Open accessAbstract
Physiological studies of CA3→CA1 synaptic transmission and plasticity have revealed both pre- and postsynaptic effects. Understanding the extent to which individual presynaptic axonal boutons could provide local compartments for control of synaptic efficacy and microconnectivity requires knowledge of their three-dimensional morphology and composition. In hippocampal slices, serial electron microscopy was used to examine a nearly homogeneous population of CA3→CA1 axons in the middle of stratum radiatum of area CA1. The locations of postsynaptic densities (PSDs), vesicles, and mitochondria were determined along 75 axon segments (9.1 ± 2.0 μm in length). Synapses, defined by the colocalization of PSDs and vesicles, occurred on average at 2.7 μm intervals along the axons. Most varicosities (68%) had one PSD, 19% had 2–4 PSDs, and 13% had none. Synaptic vesicles occurred in 90% of the varicosities. One-half (53%) of the varicosities lacked mitochondria, raising questions about their regulation of ATP and Ca 2+, and 8% of varicosities contained only mitochondria. Eleven axons were reconstructed fully. The varicosities were oblong and varied greatly in both length (1.1 ± 0.7 μm) and volume (0.13 ± 0.14 μm 3), whereas the intervaricosity shafts were narrow, tubular, and similar in diameter (0.17 ± 0.04 μm) but variable in length (1.4 ± 1.2 μm). The narrow axonal shafts resemble dendritic spine necks and thus could promote biochemical compartmentalization of individual axonal varicosities. The findings raise the intriguing possibility of localized differences in metabolism and connectivity among different axons, varicosities, and synapses.
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Certain axonal and dendritic domains are less than 0.50 μm in diameter.
“For example, certain axonal and dendritic domains are less than 0.50 μm in diameter (Shepherd and Harris, 1998), and myelinated axons at three different sites of the corpus callosum in the human brain are estimated to have axon diameters of ≥0.50 μm, in 70–90% of cases (range 0.16–3.73 μm, mean 0.73 ± 0.55 μm) (Liewald et al., 2014).”
From Human Brain/Cloud Interface (2019) · cites this paper as Shepherd and Harris, 1998
The Axonal shafts section and Table 3 report shaft diameters averaging 0.17 μm, with a range of 0.11–0.30 μm, supporting the axonal part of the claim. The paper compares these narrow shafts to dendritic spine necks but does not give a dendritic diameter measurement below 0.50 μm. Page numbers are unavailable in our copy. (LLM, conf=0.85)
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- Authors
- Shepherd, G. M. G., & Harris, K. M.
- Affiliations
- Massachusetts General Hospital (US)
- Boston Children's Hospital (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1998-10-15
- Volume
- 18
- Issue
- 20
- Pages
- 8300-8310
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6792846
- OpenAlex
- W2124486024
- Cited by
- 502
- References
- 1
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 10 · 2023: 16 · 2022: 15 · 2021: 14 · 2020: 16 · 2019: 24 · 2018: 14 · 2017: 24 · 2016: 25 · 2015: 25 · 2014: 18 · 2013: 24 · 2012: 20
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Aeronautics and Space Administration
- National Institutes of Health (NS21184)
- National Institute of Mental Health (MH/DA 57351)
- National Institute on Drug Abuse (R01DA057351)
- National Institute of Neurological Disorders and Stroke (R01NS021184, NS21184, R37NS021184)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655, P30HD-18655)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Anatomy › Medical and Biological Sciences
- Keywords
- hippocampus, axonal varicosities, postsynaptic density, synaptic vesicles, mitochondria, axon ultrastructure, synaptic transmission, stratum radiatum, axon reconstruction
- MeSH terms
- Animals, Cell Communication, Cell Compartmentation, Hippocampus, Image Processing, Computer-Assisted, Interneurons, Male, Microscopy, Electron, Mitochondria, Organ Culture Techniques, Synaptic Vesicles, Presynaptic Terminals, Pyramidal Cells, Rats, Long-Evans, Rats
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