New Technique Offers Faster, More Accurate Way to Count Brain Cells
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Method Eases Task Vital to Explaining How Humans Differ From Other Animals
Updated Oct. 10, 2014 2:29 p.m. ET
Counting brain cells helps explain how humans differ from other animals, but until recently, enumerating billions of cells by species was too onerous a task to tackle. That changed with the work of a Brazilian researcher who pioneered a technique that is both fast and accurate.
“We’re looking at the most basic properties of brain tissue,” said Suzana Herculano-Houzel, who developed the approach. “What is it made of, what are the rules of putting a brain together, and how does the human brain compare to other brains?”
Ms. Herculano-Houzel, who heads the Laboratory of Comparative Neuroanatomy in Rio de Janeiro, has now counted the cells of 190 brains in 101 different species. Human brains, she has learned, have about 86 billion neurons, the basic unit that processes information in the brain. Mice have 71 million. And elephants have a whopping 257 billion—although relatively few are in the region of the brain associated with intelligence.
“If we had to do the type of studies she has managed to perform using the traditional approach, we would still be processing the brains,” said Patrick R. Hof, a professor of neuroscience at the Icahn School of Medicine at Mount Sinai in New York and editor of the Journal of Comparative Neurology. “It would be decades of work.”
Today’s standard technique for the postmortem analysis of brain tissue is stereology. Scientists thinly slice the brain, stain the tissue and examine samples under a microscope to determine the presence or absence of cells. The method is valuable because it preserves the structure of the cells and brain.
But analyzing a single mouse brain in this way takes several days. Examining 10 mouse brains would take 10 times as long. And exploring larger brains is even more daunting.
Ms. Herculano-Houzel’s technique is drastically different. Rather than slicing the brain into sections, she divides it into its major regions and dissolves pieces weighing about three grams each in detergent to produce a liquid that contains free-floating nuclei.
She then agitates the liquid to evenly distribute the nuclei and counts the units in four samples viewed under a microscope. Cells aren’t evenly distributed in intact brain tissue, and this homogeneous “soup” makes counting easier. She averages the counts and extrapolates the total number of cells in the volume of fluid, repeating until the entire brain has been processed. The separate estimates are combined to arrive at the total number of neurons in the brain with a margin of error of about 10%.
The larger the brain, the more time it takes to process. One person can estimate the total number of neurons in a mouse brain in four hours. A human brain takes one to two months if four people share the work. An elephant brain takes six months with four people working on it.
“The quality of data that is generated is really remarkable,” Mr. Hof said. “You get extremely precise estimates of the parameters you are investigating.”
However, he notes, the process is a simple measure that reveals little about the nature of the neurons, and nothing about their activity or how they are connected —puzzles that other scientists, including this week’s Nobel Prize winners in physiology or medicine, are trying to unravel.
Ms. Herculano-Houzel focuses her research on comparing species, but her method also has implications for other areas of study. For example, Jon Kaas, a psychology professor at Vanderbilt University who studies brain architecture, has used it to compare the brains of healthy baboons to ones with epilepsy.
“There was a huge difference in the motor area of the cortex,” Mr. Kaas said. “The baboons with epilepsy had lost a large number of neurons, but you wouldn’t have guessed that from their behavior. They were compensating.”
Mr. Kaas hopes the findings, which were published last year in the Proceedings of the National Academy of Sciences, will guide research on preventing the disease.
So far, Ms. Herculano-Houzel has examined four human brains, including three from men in their 50s and one from a man in his 70s. Additional brains could alter the average, but because the human brain contains so many more neurons than nearly any other species, normal variations wouldn’t affect conclusions about the differences between humans and other species.
For example, by Ms. Herculano-Houzel’s count, humans have 16 billion neurons in the cerebral cortex, where conscious thought occurs—more than any other animal. The elephant brain, in contrast, has only 5.6 billion neurons in the cerebral cortex. Nearly all of its other neurons are concentrated in the cerebellum, where fine motor skills are controlled, perhaps for the purpose of operating the animal’s massive trunk.
Differences like these, Ms. Herculano-Houzel said, help explain the cognitive superiority of humans.
“If you look at the sheer number of neurons,” she said, “it’s got to be one of the most remarkable reasons for us not acting as great apes.”
Or, to put it another way, counting the number and distribution of neurons in the brain helps answer the age-old question: Are you a man or a mouse? |
