Precocious and delayed neocortical synaptogenesis in fetal holoprosencephaly
Bibliographic record
Abstract
Predictable temporal and spatial patterns of synaptophysin expression previously were demonstrated in the normally developing fetal cerebral cortex, reflecting synaptogenesis without regard to neurotransmitters. We studied 6 human fetal brains with holoprosencephaly in the mid-2nd and 3rd trimesters with immunocytochemical antibodies against synaptophysin and other markers of neuronal maturation. We found not only abnormal patchy patterns of synaptic vesicle reactivity within the disorganized cortical plate, but also loss of precise timing of genetically programmed synaptogenesis. Precociousness in synaptophysin reactivity relative to age-matched controls was demonstrated in 5 cases, and delayed reactivity in 1. Abnormalities were more severe in paramedian than in more lateral regions of the cerebral cortex, following a medio-lateral gradient in the horizontal axis. Extrapial heterotopia exhibited early synaptogenesis. The nodular histological architecture of paramedian zones of cortex contains randomly oriented branching micro-columns of neurones, a unique feature. The hippocampus and subcortical structures did not show precocious synapses, except for delay in the case of cortical synaptic delay. We conclude that synaptic precociousness occurs often in holoprosencephaly but is limited to the cerebral cortex; synaptic delay occurs in others. Precociousness may limit synaptic plasticity and contribute to earlier epileptogenic circuitry. Faulty genetic programming alters not only cortical histological architecture but also the timing of onset of synapse formation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".