Exploration forges differences in identical twins

Same genes, same environment, different behavior.

Identical twin mice sharing the same mazelike environment develop distinct personalities based on how much they explore their surroundings, researchers report in the May 10 Science. After death, those differences were reflected in the animals’ brains.

The study “highlights something for which we had some intuition before, but actually quantifies it,” says Fred Gage, a neuroscientist at the Salk Institute for Biological Studies in La Jolla, Calif.

Some character and biological differences between identical twins may originate as early as pregnancy. But twins become more and more different as life goes on, even when they grow up together. Scientists have recognized that having distinct experiences within the same environment might boost such personality differences, but that’s difficult to test in humans.

Studying it in animals has multiple benefits. “You can keep the genes constant and also keep the environment constant,” says Gerd Kempermann of the Center for Regenerative Therapies Dresden in Germany. “It’s much more controlled than in a human situation.”

Researchers led by Kempermann put 40 genetically identical female mice in an elaborate cage and observed their behavior. The cage had multiple levels linked together by tubes and contained toys and other features that the animals could explore. The researchers equipped each mouse with a microchip that tracked its location, using the animals’ movements as a measure of exploratory behavior. Initially, the mice differed only slightly in their tendency to roam. As they grew older, all tended to explore more often, but the differences among the mice grew more pronounced.

After three months, the researchers removed and cross-sectioned the animals’ brains, counting how many neurons were spawned in the hippocampus, a brain region important in navigation and memory. Neuron generation — which helps the hippocampus adapt to complex environments and experiences — is relatively easy to observe and quantify, Kempermann says.

As a control, researchers did the same experiment on mice in a cage that had fewer toys, twists and turns. On average, mice in the richer experimental environment generated about three times as many neurons in their hippocampi as the control mice did. That suggested that the complex environment itself could promote neuron generation.

Within the test group, some of the mice explored a wider area than others did. The more the mice explored, the more new neurons they generated on average, the researchers found. While it’s not clear that the exploring was what caused the boost in neurons, Kempermann says, further experiments in which researchers manipulate mice’s behavior and observe neuron generation, or vice versa, could demonstrate cause-and-effect.

Despite being genetically identical, the mice weren’t behaviorally identical to begin with: They almost certainly had subtle brain differences that made some want to explore more than others, Gage notes. “What’s interesting for me is, what is that initiating event that contributes to the differences?”

Kempermann and colleagues say a whole host of factors could produce these differences, but they don’t know which ones are the main culprits. Among the possibilities are gene mutations arising after conception, differences in feeding, position in the uterus and epigenetic effects — the environment’s influence on gene activity through chemical modifications that don’t change the genes themselves.