One gene turns low-ranking mice into alpha-rodents

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Two mice run headfirst into one another in a narrow plastic tube that isn’t wide enough for both of them. One of them must give way. In their earlier encounter, the first mouse exerted its dominance by forcing its rival to reverse down the tube. This time, things are different; the second mouse pulls rank and the first one backs down.

Mouse hierarchies don’t change this readily, but the second mouse has been given a boon by Fei Wang at the Chinese Academy of Science. By injecting a single gene into one part of its brain, Wang turned the subordinate animal into a dominant one.

The gene that gave the mouse a burst of social mobility is GluR4. It creates part of a protein called the AMPA receptor, which allows signals to flow quickly between two neurons. By injecting extra GluR4 into a mouse’s brain, and producing more AMPA receptors, Wang strengthened the connections between its neurons. The effect is like building expressways between two cities overnight – you can have a much larger and faster flow of traffic between them.

Wang injected the extra GluR4 into a part of the rodents’ brains called the medial prefrontal cortex (mPFC), which has been linked to social rank. As early as 1986, scientists showed that rats lose their social status if they suffer injuries to their mPFCs. Wang himself found that the mPFC’s neurons signal more strongly to one another in dominant brains than in subordinate ones.

By manipulating this signalling, he could push mice up or down the social ladder. With an extra dose of GluR4, the mice gained social standing. When they confronted other mice in a cramped plastic tube, they were more likely to force their rivals to retreat, even if they had previously given way. With their new rank, they were also more likely to court female mice with high-pitched ultrasonic songs.

On the flipside, Wang managed to lower the rodents’ rank by injecting them with just a small fragment of GluR4 (GluR4Ct). On its own, this fragment scuppers AMPA receptors and weakens the communication lines between the mPFC’s neurons. This time, the newly subordinate mice were more likely to give way to individuals that they had previously bested, and they were less likely to sing to females.

How could changes in the brain of one animal affect its standing among its peers? Wang thinks that the answer lies with the mPFC. Among other roles, this region has been linked to social behaviour and hierarchies, in humans as well as mice. When computer gamers think about players who are better than they are, their mPFCs light up.

The mPFC acts like a control centre for social interactions. It exerts influence over other parts of the brain that release hormones and signalling chemicals, which affect everything from aggressiveness to fear. If you change the strength of the signals in the mPFC, the effects would ripple out across the brain. Perhaps the mice become more aggressive; maybe they become less fearful. Wang is now looking at which of these effects accounts for the rise and fall of the rodents’ ranks.

We’ve known that animals form dominance hierarchies for around a century. In 1921, Norwegian scientist Thorleif Schjelderup-Ebbe discovered one of the first examples of these hierarchies in chickens, which is why they’re more commonly known as pecking orders. They’re a vital part of animal life. An individual’s rank can drastically affect its access to mates, food and shelter. These ranks emerge very early (you can see them in two-year-old children) and they change very slowly, if at all.

But very few people have looked at how different social ranks are manifested in the brain. Wang has not only started to do that, but he has shown that manipulating the brain can actually change a mouse’s rank. It would be fascinating (and probably experimentally tricky) to see if the same trick would work in humans. It is unlikely though, especially since our social structures are much more complex. For a mouse, it’s enough to give it an extra gene that makes it pushier. We have wealth, reputation, contacts, education and discrimination to contend with.

Reference:
Wang, F., Zhu, J., Zhu, H., Zhang, Q., Lin, Z., & Hu, H. (2011). Bidirectional Control of Social Hierarchy by Synaptic Efficacy in Medial Prefrontal Cortex Science DOI: 10.1126/science.1209951