Connectomes across development reveal principles of brain maturation
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Abstract
An animal's nervous system changes as its body grows from birth to adulthood and its behaviours mature 1-8. The form and extent of circuit remodelling across the connectome is unknown 3,9-15. Here we used serial-section electron microscopy to reconstruct the full brain of eight isogenic Caenorhabditis elegans individuals across postnatal stages to investigate how it changes with age. The overall geometry of the brain is preserved from birth to adulthood, but substantial changes in chemical synaptic connectivity emerge on this consistent scaffold. Comparing connectomes between individuals reveals substantial differences in connectivity that make each brain partly unique. Comparing connectomes across maturation reveals consistent wiring changes between different neurons. These changes alter the strength of existing connections and create new connections. Collective changes in the network alter information processing. During development, the central decision-making circuitry is maintained, whereas sensory and motor pathways substantially remodel. With age, the brain becomes progressively more feedforward and discernibly modular. Thus developmental connectomics reveals principles that underlie brain maturation.
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It is likely that some weak connections persist across individuals.
“Although some of these low-synapse-number connections may be spurious, it is likely that some weak connections persist across individuals, as has been found in C. elegans27.”
From Network statistics of the whole-brain connectome of Drosophila (2024) · cites this paper as [27]
In C. elegans, there is substantial variability in the connectomes of genetically identical individuals.
“In C. elegans, there is substantial variability in the connectomes of genetically identical individuals27.”
From Network statistics of the whole-brain connectome of Drosophila (2024) · cites this paper as [27]
Connectomes in C. elegans have been proofread to the level of individual synapses, but this is not feasible in larger datasets.
“While connectomes in C. elegans have been proofread to the level of individual synapses21,27,35, this is not feasible in larger datasets2,3,31.”
From Network statistics of the whole-brain connectome of Drosophila (2024) · cites this paper as [27]
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- Authors
- Witvliet, D., Mulcahy, B., Mitchell, J. K., Meirovitch, Y., Berger, D. R., Wu, Y., Liu, Y., Koh, W. X., Parvathala, R., Holmyard, D., Schalek, R. L., Shavit, N., Chisholm, A. D., Lichtman, J. W., Samuel, A. D. T., & Zhen, M.
- Affiliations
- Mount Sinai Hospital (CA)
- Harvard University (US)
- MIT Computer Science and Artificial Intelligence Laboratory (US)
- University of California San Diego (US)
- Corresponding author
- Witvliet, Daniel
- Lichtman, Jeff W.
- Samuel, Aravinthan D. T.
- Zhen, Mei
- ORCID
- Venue
- Nature
- Published
- 2021-08-04
- Volume
- 596
- Issue
- 7871
- Pages
- 257-261
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC8756380
- OpenAlex
- W3192789395
- Cited by
- 393
- References
- 5
- Citations by year
- 2026: 69 · 2025: 70 · 2024: 86 · 2023: 73 · 2022: 56 · 2021: 32 · 2020: 7
- FWCI
- 28.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (P50MH094271)
- National Institute of Neurological Disorders and Stroke (UF1NS111697, U24NS109102, R01NS082525, U19NS104653)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- brain maturation, Caenorhabditis elegans, connectome, synaptic connectivity, postnatal development, feedforward neural networks, brain modularity, serial section electron microscopy
- MeSH terms
- Aging, Animals, Brain, Individuality, Interneurons, Microscopy, Electron, Models, Neurological, Neural Pathways, Neurons, Stereotyped Behavior, Synapses, Caenorhabditis elegans, Connectome
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