Ultrastructural analysis of adult mouse neocortex comparing aldehyde perfusion with cryo fixation
Open accessAbstract
Analysis of brain ultrastructure using electron microscopy typically relies on chemical fixation. However, this is known to cause significant tissue distortion including a reduction in the extracellular space. Cryo fixation is thought to give a truer representation of biological structures, and here we use rapid, high-pressure freezing on adult mouse neocortex to quantify the extent to which these two fixation methods differ in terms of their preservation of the different cellular compartments, and the arrangement of membranes at the synapse and around blood vessels. As well as preserving a physiological extracellular space, cryo fixation reveals larger numbers of docked synaptic vesicles, a smaller glial volume, and a less intimate glial coverage of synapses and blood vessels compared to chemical fixation. The ultrastructure of mouse neocortex therefore differs significantly comparing cryo and chemical fixation conditions.
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Recent data with high-pressure cryopreservation show much less astrocytic coverage of both capillaries and synapses than seen with aldehyde fixation.
“however, recent data with high-pressure cryopreservation show much less astrocytic coverage of both capillaries and synapses than seen with aldehyde fixation, which shrinks the extracellular space (Korogod et al., 2015).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Korogod et al., 2015
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- Authors
- Korogod, N., Petersen, C. C., & Knott, G. W.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Petersen, Carl CH
- Knott, Graham W
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2015-08-11
- Volume
- 4
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC4530226
- OpenAlex
- W1926373965
- Cited by
- 408
- References
- 63
- Citations by year
- 2026: 22 · 2025: 38 · 2024: 55 · 2023: 54 · 2022: 38 · 2021: 48 · 2020: 41 · 2019: 32 · 2018: 28 · 2017: 27 · 2016: 20 · 2015: 5
- FWCI
- 12.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Schweizerische Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Human Frontier Science Program (HFSP)
- European Research Council (ERC)
- 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
- Health Sciences › Medicine › Anatomy › Medical and Biological Sciences
- Keywords
- neocortex, cryofixation, chemical fixation, high-pressure freezing, extracellular space, synaptic vesicles, synapses, blood vessels, tissue deformation
- MeSH terms
- Aldehydes, Animals, Fixatives, Freezing, Microscopy, Electron, Perfusion, Tissue Fixation, Neocortex, Mice
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