The search for true numbers of neurons and glial cells in the human brain: A review of 150 years of cell counting

• Published in: Journal of comparative neurology (1911) Vol. 524; no. 18; pp. 3865 - 3895
• Main Authors: von Bartheld, Christopher S., Bahney, Jami, Herculano-Houzel, Suzana
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 15.12.2016; Wiley Subscription Services, Inc
• Subjects: Animals; Brain - cytology; Cell Count - history; Cell Count - methods; cell counts; glia number; glia-neuron ratio; history; History, 19th Century; History, 20th Century; History, 21st Century; human brain; Humans; Neuroglia - cytology; neuron number; Neurons - cytology; quantification; cell counts; human brain; quantification; glia-neuron ratio; history; neuron number; glia number
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.24040

ABSTRACT For half a century, the human brain was believed to contain about 100 billion neurons and one trillion glial cells, with a glia:neuron ratio of 10:1. A new counting method, the isotropic fractionator, has challenged the notion that glia outnumber neurons and revived a question that was widely thought to have been resolved. The recently validated isotropic fractionator demonstrates a glia:neuron ratio of less than 1:1 and a total number of less than 100 billion glial cells in the human brain. A survey of original evidence shows that histological data always supported a 1:1 ratio of glia to neurons in the entire human brain, and a range of 40–130 billion glial cells. We review how the claim of one trillion glial cells originated, was perpetuated, and eventually refuted. We compile how numbers of neurons and glial cells in the adult human brain were reported and we examine the reasons for an erroneous consensus about the relative abundance of glial cells in human brains that persisted for half a century. Our review includes a brief history of cell counting in human brains, types of counting methods that were and are employed, ranges of previous estimates, and the current status of knowledge about the number of cells. We also discuss implications and consequences of the new insights into true numbers of glial cells in the human brain, and the promise and potential impact of the newly validated isotropic fractionator for reliable quantification of glia and neurons in neurological and psychiatric diseases. J. Comp. Neurol. 524:3865–3895, 2016. © 2016 Wiley Periodicals, Inc. The number of glial cells in human brains has been vastly overestimated. The real number of glia is in fact lower than the number of neurons. The origin, perpetuation, and the debunking of the claim of one trillion glial cells in human brains are the topics of this review.