Synaptic development in the human fetus: A morphometric analysis of normal and Down's syndrome neocortex
Abstract
Postmortem tissue was obtained from six normal and four Down's syndrome brains ranging in age from 12 to 40 weeks postconception. Tissue was processed for electron microscopy using routine osmium and EPTA staining procedures, and to examine synaptic development, photomicrographs were systematically taken throughout the molecular layer of the sensorimotor neocortex. The number of EPTA-stained synapses were consistently greater than the number of osmium-stained synaptic contacts. A progressive increase in synaptic density throughout the range of ages examined was observed for both normal and Down's syndrome tissue. There was also an increase with developmental age in apparent measures of synaptic maturity, e.g., an increased ratio of mature to primitive contacts and asymmetrical to symmetrical contacts. In normal tissue, pre- and postsynaptic membrane lengths were observed to increase with the ages studied, whereas synaptic membrane widths appeared to attain mature values by 29 weeks postconception. Cleft width remained fairly constant to 28 weeks postconception. Although direct statistical comparisons could not be made, in Down's tissue synaptic parameter development was generally less consistent and the parameters appeared to be reduced during the later stages of development studied.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The sole electron microscopic study of the fetal brain of individuals with Down syndrome reports that the synapse density of cortical neurons is comparable in individuals with Down syndrome and controls at midfetal stages, but that measures of synaptic morphology such as the width and length of the post-synaptic density are reduced during late fetal development.
“In fact, the sole electron microscopic study of the fetal brain of individuals with DS119 reports that the synapse density of cortical neurons is comparable in individuals with DS and controls at midfetal stages, but that measures of synaptic morphology — such as the width and length of the post-synaptic density — are reduced during late fetal development (Fig. 3b).”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [119]
Such findings support the suggestion that synaptic deficits are present at early developmental stages in Down syndrome, but the limited resolution of the techniques used in some of these investigations precludes the drawing of specific conclusions.
“Such findings support the suggestion that synaptic deficits are present at early developmental stages in DS, but the limited resolution of the techniques used in some of these investigations preclude the drawing of specific conclusions.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [119]
Neonatal DS brain tissue has a higher percentage of primitive synaptic contacts than control tissue.
“Through electron microscopy of neonatal DS and control brains, this study reveals a higher percentage of primitive synaptic contacts in the DS tissue.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [119]
Cites
Structural abnormalities of the cerebral cortex in human chromosomal aberrations: a Golgi study
Marin-Padilla, M. (1972) · Brain Research · doi:10.1016/0006-8993(72)90324-1 · Cited by 290 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Apoptosis and increased generation of reactive oxygen species in Down's syndrome neurons in vitro
Busciglio, J., & Yankner, B. A. (1995) · Nature · doi:10.1038/378776a0 · Cited by 741 · see citing works
Dendritic atrophy in children with down’s syndrome.
Becker, L. E., Armstrong, D. L., & Chan, F. (1986) · Annals of Neurology · doi:10.1002/ana.410200413 · Cited by 279 · see citing works
Self-citationChanges in synaptic density in motor cortex of rhesus monkey during fetal and postnatal life
Zecevic, N., Bourgeois, J.-P., & Rakic, P. (1989) · Developmental Brain Research · doi:10.1016/0165-3806(89)90124-7 · Cited by 253 · see citing works
Chakrabarti, L., Galdzicki, Z., & Haydar, T. F. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3406-07.2007 · Cited by 199 · see citing works
In vivo modeling of human neuron dynamics and Down syndrome
Real, R., Peter, M., Trabalza, A., Khan, S., Smith, M. A., Dopp, J., Barnes, S. J., Momoh, A., Strano, A., Volpi, E., et al. (2018) · Science · doi:10.1126/science.aau1810 · Cited by 120 · see citing works
Aziz, N. M., Guedj, F., Pennings, J. L. A., Olmos-Serrano, J. L., Siegel, A., Haydar, T. F., & Bianchi, D. W. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.031013 · Cited by 118 · see citing works
Evidence of Arrest of Neurogenesis and Synaptogenesis in Brains of Patients with Down's Syndrome
(1984) · New England Journal of Medicine · doi:10.1056/nejm198411013111819 · Cited by 82 · see citing works
Consequences of trisomy 21 for brain development in Down syndrome
Russo, M. L., Sousa, A. M. M., & Bhattacharyya, A. (2024) · Nature Reviews Neuroscience · doi:10.1038/s41583-024-00866-2 · Cited by 28 · see citing works
“In fact, the sole electron microscopic study of the fetal brain of individuals with DS 119 reports that the synapse density of cortical neurons is comparable in individuals with DS and controls at midfetal stages, but that measures of synaptic morphology — such as the width and length of the…”
Concurrent Generation of Subplate and Cortical Plate Neurons in Developing Trisomy 16 Mouse Cortex
Cheng, A., Haydar, T. F., Yarowsky, P. J., & Krueger, B. K. (2004) · Developmental Neuroscience · doi:10.1159/000082142 · Cited by 22 · see citing works
Postnatal Cerebral Maturation in Down's Syndrome Children: A Developmental Eeg Coherence Study
McAlaster, R. (1992) · International Journal of Neuroscience · doi:10.3109/00207459209003296 · Cited by 22 · see citing works
Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex
Risgaard, R. D., Hanthanan Arachchilage, K., Knaack, S. A., Hosseini, M., Chen, R. J., Kumarage, P., Schmidt, D. K., Huang, X., Sheng, J., Wang, C. J., et al. (2026) · Science · doi:10.1126/science.aea1549 · Cited by 12 · see citing works
- Authors
- Petit, T. L., LeBoutillier, J. C., Alfano, D. P., & Becker, L. E.
- Affiliations
- University of Toronto (CA)
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 1984-01
- Volume
- 83
- Issue
- 1
- Pages
- 13-23
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2048103749
- Cited by
- 84
- References
- 1
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 1 · 2018: 5 · 2017: 1 · 2016: 3 · 2015: 1 · 2013: 3 · 2012: 1
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- synaptic development, Down syndrome, sensorimotor cortex, synaptic density, synapse maturation, synaptic asymmetry, synaptic cleft width, postconceptional age, human fetal brain
- MeSH terms
- Down Syndrome, Fetus, Humans, Somatosensory Cortex, Synapses
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review