New insights into the molecular architecture of neurons by cryo-electron tomography
Open accessAbstract
Cryo-electron tomography (cryo-ET) visualizes natively preserved cellular ultrastructure at molecular resolution. Recent developments in sample preparation workflows and image processing tools enable growing applications of cryo-ET in cellular neurobiology. As such, cryo-ET is beginning to unravel the in situ macromolecular organization of neurons using samples of increasing complexity. Here, we highlight advances in cryo-ET technology and review its recent use to study neuronal architecture and its alterations under disease conditions.
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Several studies have imaged neuronal processes by cryo-EM and cryo-ET, showing neurites are accessible to cryogenic imaging but persistent challenges remain at molecular resolution due to poor contrast and cytoplasmic denseness.
“Several studies have imaged neuronal processes by cryo-EM and cryo-ET19–25, showing that neurites are accessible to cryogenic imaging, while also revealing persistent challenges in obtaining information at a molecular resolution due to poor contrast and cytoplasmic denseness.”
From Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons (2026) · cites this paper as [20]
Cites
Quantitative analysis of the native presynaptic cytomatrix by cryoelectron tomography
Fernández-Busnadiego, R., Zuber, B., Maurer, U. E., Cyrklaff, M., Baumeister, W., & Lučić, V. (2010) · Journal of Cell Biology · doi:10.1083/jcb.200908082 · Cited by 267 · see citing works
Self-citationThe postsynaptic density in excitatory synapses is composed of clustered, heterogeneous nanoblocks
Sun, R., Allen, J. P., Mao, Z., Wilson, L., Haider, M., Alten, B., Zhou, Z., Wang, X., & Zhou, Q. (2025) · Journal of Cell Biology · doi:10.1083/jcb.202406133 · Cited by 20 · see citing works
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Bodakuntla, S., Marelli, J., Vasquez-Montes, V., Glauser, S., Biertümpfel, C., & Mizuno, N. (2026) · Nature Communications · doi:10.1038/s41467-026-77741-4
- Authors
- Petrovic, A., Do, T. T., & Fernández-Busnadiego, R.
- Affiliations
- Universitätsmedizin Göttingen (DE)
- Venue
- Current Opinion in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2025-02
- Volume
- 90
- Pages
- 102939
- ISSN
- 0959-4388 (ISSN-L)
- OpenAlex
- W4405264869
- Cited by
- 4
- References
- 2
- Citations by year
- 2026: 2 · 2025: 2
- FWCI
- 0.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Opinion in Neurobiology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (publishedVersion, other-oa)
- Funders
- German Research Foundation (SFB1286/A12, EXC 2067/1- 390729940)
- European Research Council
- HORIZON EUROPE European Research Council (CoG 101088355)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- cryo-electron tomography, neuronal architecture, macromolecular organization, neurodegeneration, neuronal ultrastructure
- MeSH terms
- Animals, Humans, Neurons, Cryoelectron Microscopy, Electron Microscope Tomography
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