Researchers hoping to study the Neanderthal brain have to face the limiting notion of studying a practical void, the empty space inside a skull that is hundreds of thousands of years old.

Geneticists at the University of California San Diego have found a way to bypass this problem by creating a miniature version of the brain inside the head of a homo neanderthalensis.

Neanderthal Minibrain In A Dish

Neanderthals are the closest extinct hominin relatives of the modern human. They had stocky, brawny bodies and brains almost as big as that of the homo sapiens. Although they were the original cavemen, Neanderthals used a sophisticated system of symbolic language not evident in other species of humans.

By extracting the ancient DNA from the fossilized remains of a Neanderthal and infusing it into an artificially grown mini-brain made from stem cells, the researchers were able to build a miniature version of the Neanderthal brain, which they hope would be able to run little robots shaped like crabs one day.

"We're trying to recreate Neanderthal minds," says Alysson Muotri, a geneticist at the School of Medicine who presented his team's findings at the Imagination and Human Evolution conference at the Salk Institute for Biological Studies in La Jolla, San Diego, California.

Using stem cells harvested from human skin cells, Muotri's team was able to build a mass of brain cells that mimic the cortex, or the outermost layer of the brain. This is called an organoid. They then injected the organoid with Neanderthal DNA, forming what the researchers call a Neanderoid.

How Researchers Built A Neanderoid

The researchers set their sights on a gene called NOVA1, one of several protein-coding genes that are different between Neanderthals and homo sapiens. NOVA1 is associated with autism and schizophrenia in modern humans.

It is also believed to have been influential in the creation of a hundred brain proteins unique to the Neanderthal. NOVA1 has only one DNA base pair that differs between Neanderthals and modern humans.

The researchers started with skin cells sampled from a person with no known neurological disorder stemming from the genes. They then engineered the skin cells to become pluripotent stem cells or stem cells that could grow into any specialized cell.

By using CRISPR gene editing, the team replaced the target human base pair in NOVA1 with one from the ancient DNA. To make sure no mutations grew from possible errors, the researchers had to sequence the cells used to build the Neanderoids.

Resulting Mini-Brain

The end result is a Neanderthal mini-brain shaped like a popcorn. The human brain organoid is more spherical in shape.

Compared to the human organoid, the Neanderoid's neuronal cells move faster to form the mini-brains' structures. The researchers have yet to pinpoint an exact reason for this, but they believe it has something to do with the Neanderoid's unique shape. It also has fewer synaptic connections or the links between nerve cells in the brain.

Muotri, who has a stepson with autism, says the differences in the Neanderoid are similar to some of the features he found in the brains of autistic children.

"I don't want families to conclude that I'm comparing autistic kids, to Neanderthals, but it's an important observation," he says. "In modern humans, these types of changes are linked to defects in brain development that are needed for socialization."

So far, the researchers have been able to spot oscillating electric signals in the Neanderoid. They hope to take their creation and hook them up to little robots resembling crabs. They hope the Neaderthal mini-brains will be able to control the robots' functions and movements.

Photo: Paul Hudson | Flickr

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