For over half a century, neuroscientists operated under the assumption that the human brain contains around 100 billion neurons and over 1 trillion glial cells.
This oft-cited “fact” made its way into textbooks and became common knowledge despite a lack of strong evidence.
Recent advances in cell counting techniques have now debunked this myth, showing that the ratio of glial cells to neurons in the brain is actually close to 1:1.
This miscalculation highlights the need for careful quantitative studies and skepticism of claims not backed by data.
Key Facts:
- The notion of a 10:1 ratio of glial cells to neurons originated in the 1950s and 60s from speculation, not data.
- Textbooks and prominent neuroscientists treated this idea as fact for decades without citing primary sources.
- More rigorous histology studies in the 1980s arrived at glial cell estimates below 100 billion, incompatible with a 10:1 ratio.
- Improved cell counting methods in the 2000s, like the isotropic fractionator, empirically measured the ratio as approximately 1:1.
Source: J Comp Neurol.
The Glia Neuron Ratio – From Speculation to “Textbook Fact”
In the mid 20th century, quantitative analysis of the cellular composition of the human brain was still in its infancy.
Many textbooks nevertheless confidently stated that the brain contains around 100 billion neurons and over 10 times as many glial cells – well over 1 trillion.
But where did this pervasive idea come from?
Famed neuroscientist Valentin von Economo empirically estimated in 1925 that the cerebral cortex alone contained over 10 billion neurons.
Just a decade later, other researchers began to assert that glia outnumbered neurons by about 10-fold throughout the brain, implying neuron counts must be around 10 billion.
Influential Swedish neurochemist Holger Hyden in 1960 proclaimed that “the glial cells outnumber the nerve cells by a factor of around 10.”
Over the next decades, through repetition in reviews and textbooks like Noback’s Human Nervous System, this claim became engrained as fact despite weak evidence.
Sources like Kuffler & Nicholls’ From Neuron to Brain and eventually Kandel et al.’s Principles of Neural Science treated the supposed 10:1 ratio as established truth.
These ideas spread unchecked partly due to a lack of skepticism and failure to trace back primary sources.
Challenges in Brain Cell (Neuron) Counting
Cell counting in the brain presents numerous technical hurdles. Neurons vary greatly in size and shape.
Glia and small neurons like cerebellar granule cells can be virtually indistinguishable.
Complex 3D structure makes representative sampling difficult.
Many early studies relied on subjective identification of cell types and extrapolation from limited samples.
Advanced techniques like stereology addressed some issues but were still prone to bias.
Immunohistological staining greatly improved cell type discrimination but brought its own limitations.
DNA content analysis sidesteps morphological identification but depends on full extraction and accurate genome size knowledge.
No approach is foolproof; validating against 3D reconstruction of all cells in a region remains the gold standard.
Even into the 1990s, distinguishing neurons from glia (histologically) remained a persistent challenge.
Reliability issues likely contributed to contradictory findings between studies.
More rigorous methods were needed to empirically determine average cellular composition.
Persistence of the “Trillion Brain Cells” Myth
In 1968, quantitative histological analysis by Blinkov & Glezer estimated the total number of glial cells in the human brain at 100-130 billion.
This was incompatible with 100 billion neurons and a 10:1 ratio, but the implication went unrecognized.
Stereologist Haug in the 1980s independently arrived at similar estimates of 40-50 billion glial cells and 70-80 billion neurons based on cell densities.
But again, the mismatch with accepted beliefs was not brought to light.
Textbooks continued to state as fact that glia outnumbered neurons 10-fold, without citing sources for this claim.
Through repetition by authoritative sources, the myth became entrenched conventional wisdom.
Challenging established ideas requires solid contrary evidence.
But for decades, no technique provided definitive whole-brain cell counts to debunk the myth.
New Brain Cell Counting Method Adds Clarity
In 2005, Brazilian neuroscientist Suzana Herculano-Houzel developed a novel cell counting approach called the isotropic fractionator.
This technique turns brain tissue into a homogeneous suspension of nuclei for counting, circumventing traditional limitations.
Key innovations include chemical fixation of nuclei, detergent dissociation of tissue, and fluorescent labeling of neuronal nuclei.
Compared head-to-head against other methods, the isotropic fractionator proved both accurate and efficient.
A 2009 study applied this technique to quantitatively determine for the first time the total number of cells in the human brain.
The researchers arrived at averages of 86 billion neurons and 85 billion non-neurons – a ratio of approximately 1:1, defying conventional wisdom.
The Path to Acceptance and Impact
Despite strong empirical evidence, overturning accepted ideas tends to meet resistance.
Some scientists remained skeptical due to ingrained beliefs that neuron counts were around 100 billion based on decades of misinformation.
Independent validation helps establish confidence in new techniques and discoveries that challenge old paradigms.
By the early 2010s, multiple studies corroborated the isotropic fractionator’s findings, leading most experts to gradually accept the updated 1:1 ratio.
This transition from dogma to data-driven understanding carries meaningful scientific implications.
Abundant glia were thought to be an evolutionary advantage that explained humans’ superior cognition.
But with humans possessing ordinary glia-neuron ratios, this theory is challenged.
In clinical neuroscience, improper cell ratios could point to pathology.
Accurate baselines are vital for identifying and studying neurological diseases involving atypical neural or glial numbers.
The trillion cell myth highlights the need to periodically re-validate accepted facts and update beliefs to fit the evidence.
New technology can provide clarity, but overturning assumptions requires open-mindedness.
Blindly propagating claims without scrutiny enables myths to persist and impedes scientific progress.
This case highlights the importance of referencing primary sources, critically evaluating methods, and forming conclusions only from strong data – all of which are essential for sound neuroscience.
References
- Study: The search for true numbers of neurons and glial cells in the human brain: a review of 150 years of cell counting
- Authors: Christopher S. von Bartheld et al. (2017)
