Total regional and global number of synapses in the human brain neocortex.
Level 5 - mechanism / opinion, no new human data
Postmortem human tissue stereological quantification study (bench/anatomical research)
PubMed 11418939 · doi:10.1002/syn.1083
What was done
Researchers developed an unbiased stereological method to estimate the total number of neocortical synapses in postmortem human brains. One randomly selected cerebral hemisphere per brain was stratified into four major neocortical regions. Neocortical volumes were measured using Cavalieri point-counting, and synaptic numerical density was measured using electron microscopy disectors with ethanolic phosphotungstic acid staining. Total synapse count was calculated as the product of volume and density in five young human male autopsy brains. In addition, the effect of a 2-day postmortem fixation delay was evaluated in five large mammals (one dog, one cow, three pigs).
What was found
The average total number of neocortical synapses across the five young male brains was 164 x 10^12 (coefficient of variation = 0.17). In the animal model, a 2-day postmortem delay resulted in an apparent, non-significant 3.9% reduction in synaptic numerical density. Tissue blocks accounted for the largest source of variation and workload, with block-to-block imprecision representing 66% of the total variance when using eight blocks per brain.
Why it matters
This study provides one of the first quantitative, design-based stereological baseline estimates of total synaptic abundance in the healthy human neocortex, establishing a methodological framework for comparing synaptic loss in neurological conditions.
Limits
The human sample was extremely small (n = 5) and restricted strictly to young males, preventing assessment of variation by sex or aging. Postmortem tissue changes remain a potential confounder despite the preliminary validation in animal models.
Cited by
- partial The human brain contains approximately 500 trillion synapses.