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Unbiased stereological estimation of the number of neurons in the human hippocampus
Abstract
The total numbers of neurons in five subdivisions of human hippocampi were estimated using unbiased Stereological principles and systematic sampling techniques. The method addresses the problems associated with the results and conclusions of previous quantitative studies, virtually all of which have been based on biased estimates of neuron densities. For each subdivision, the total number of neurons was calculated as the product of the estimate of the volume of the neuron‐containing layers and the estimate of the numerical density of neurons in the layers. Each hippocampus was cut into 3‐mm‐thick slabs, transverse to the rostrocaudal axis. One 70‐μUm‐thick section from each slab was used in the analysis. The volumes of the layers containing neurons in five major subdivisions of the hippocampus (granule cell layer, hilus, CA3–2, CA1, and subiculum) were estimated with point‐counting techniques after delineation of the layers on each section. The numerical densities of neurons in each subdivision were estimated on the same sections with optical directors. The sampling used in both estimates was performed systematically in all three dimensions. In an example of five hippocampi, the mean numbers of neurons (CV = SD/mean) in the different subdivisions were as follows: granule cells 15 × 10 6 (0.28), hilus 2.0 × 10 6 (0.16), CA3‐2 2.7 × 10 6 (0.22), CA1 16 × 10 6 (0.32), subiculum 4.5 × 10 6 (0.19). The stereological measurements contributed approximately 25% of the observed variance. Among the five subjects there was a significant inverse relationship between age (which ranged from 47 to 85 years) and the total number of neurons in CA1 (which ranged from 24 to 11 × 10 6). An optimized sampling scheme for studies of the number of neurons in the human hippocampus has been designed on the basis of an analysis of variance of the estimates at different levels of the sampling scheme. Counting neurons in the five subdivisions of the human hippocampus with the optimized sampling scheme takes less than 4 hours.
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“The coefficients of error (CE) were calculated according to the procedure of Gunderson and colleagues as estimates of precision [66]. The values of CE were 0.047 ± 0.006667 (Gunndersen m = 0) for pSer-129+ cells and 0.063 ± 0.012 (Gunndersen m = 0) for GFP+ cells in NHPs, and 0.105 ± 0.0087 GFP+ cells for rats.”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [66]
In the citing paper
“In order to estimate the number cells transduced by Olig001, GFP+ or pSer-129+ cells in rats and monkeys in an unbiased fashion, stereological counting methods [66] using the optical fractionator probe in Stereo Investigator (Microbrightfield Bioscience, Version10.40) were applied.”
From Novel oligodendroglial alpha synuclein viral vector models of multiple system atrophy: studies in rodents and nonhuman primates (2017) · cites this paper as [66]
In the citing paper
“To ensure that the estimation was unbiased, the first section plane was placed randomly within the first interval length (West and Gundersen, 1990).”
From Profound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease (1996) · cites this paper as West and Gundersen, 1990
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Cited by
Sorted by citations
West, M. J., Slomianka, L., & Gundersen, H. J. G. (1991) · The Anatomical Record · doi:10.1002/ar.1092310411 · Cited by 2,994
“Vref scheme has the disadvantage that the shrinkage or expansion that occurs between the preparation of the blocks and the analysis of the sections must be known and that the sectional area of the extensive thin layers, like the dentate granule cell layer must be estimated with a somewhat involved point counting schem…”
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“Detailed descriptions of these techniques have been presented elsewhere (West and Gundersen, 1990).”
MethodInfluentialReconstruction and Simulation of Neocortical Microcircuitry
Markram, H., Muller, E., Ramaswamy, S., Reimann, M. W., Abdellah, M., Sanchez, C. A., Ailamaki, A., Alonso-Nanclares, L., Antille, N., Arsever, S., et al. (2015) · Cell · doi:10.1016/j.cell.2015.09.029 · Cited by 1,557
“Layer boundaries and densities per layer were computed on slices using optical dissectors on NeuN-stained tissue (West and Gundersen, 1990; Williams and Rakic, 1988) and Stereo Investigator software (StereoInvestigator 7.”
Method
Metadata
- Authors
- West, M. J., & Gundersen, H. J. G.
- Affiliations
- Aarhus University (DK)
- Corresponding author
- West, Mark J.
- ORCID
- West, Mark J.
- Venue
- Journal of Comparative Neurology
- Publisher
- Wiley
- Published
- 1990-06
- Volume
- 296
- Issue
- 1
- Pages
- 1-22
- ISSN
- 0021-9967 (ISSN-L)
- 1096-9861
- OpenAlex
- W2014892312
- Cited by
- 1,153
- References
- 47
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 10 · 2023: 17 · 2022: 24 · 2021: 22 · 2020: 24 · 2019: 19 · 2018: 40 · 2017: 27 · 2016: 32 · 2015: 30 · 2014: 38 · 2013: 40 · 2012: 41
- FWCI
- 46.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Comparative Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sundhed og Sygdom, Det Frie Forskningsråd
- Topics
- Physical Sciences › Mathematics › Applied Mathematics › Point processes and geometric inequalities
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Anatomy › Classical Anatomy and Histology
- Keywords
- human hippocampus, neuron number estimation, neuronal density, unbiased stereology, optical disector, point counts, CA1, CA3, subiculum, granular layer, hilus, age-related neuronal loss
- MeSH terms
- Aged, Aged, 80 and over, Cell Count, Hippocampus, Humans, Middle Aged
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