A Study of Unfaithful Voles Links Genes to Brains to Behaviour

Prairie voles are meant to be models of monogamy. These adorable rodents form intense lifelong bonds, sticking with the same partner year after year, and raising many generations of pups together. But monogamy doesn’t mean fidelity. Male prairie voles will “cheat” on their partners, wandering into neighbouring territories and mating with females from other couples. And the males differ (#notallvoles?), in that  some individuals are steadfastly faithful while others are more likely to stray.

Now, Steven Phelps from the University of Texas at Austin has shown how these differences in behaviour are connected to differences in the voles’ genes. Specifically, males can inherit variants of a particular gene that affect a part of the brain involved in remembering places. If they have variants that confer poorer spatial memory, they are worse at remembering the locations of social encounters, more likely to wander out of their own territories, more likely to meet other females, and more likely to have pups out of volelock.

Phelps’ study does what few others do: It weaves threads that connect genetics, neuroscience, psychology, and evolutionary biology. It shows how a few DNA differences can change the molecules in an animal’s brain, dramatically changing its social behaviour in ways that affect its success at siring the next generation. It’s a bravura piece of work.

Scientists have been studying the social lives of prairie voles since 1971, when Lowell Getz first discovered their long-term bonds. Together with neurobiologist Sue Carter, he showed that these bonds depends on two related hormones called oxytocin and vasopressin, which are involved in many kinds of social behaviours.

Let’s focus on vasopressin. It works by docking into a protein called the vasopressin receptor, like a key fitting into a lock. The receptor is crucial. The monogamous prairie voles have higher levels of it than promiscuous relatives like meadow voles. If you block it, you block the strong bonds between prairie couples. And if you load extra copies of it into the brains of meadow voles, you can convert them to the monogamous ways of their prairie relatives.

Back in 2003, Phelps and Larry Young caught wild prairie voles and marked the locations of the vasopressin receptor in their brains. “We were shocked by how diverse their brains were. It seemed like every animal was a snowflake,” Phelps recalls. “I showed the images to Tom Insel and he literally laughed. He said, ‘You’ve got a couple of species here. This can’t just be prairie voles.’ But sure enough, the genetics confirmed that they were all prairie voles. They were just really diverse.”

Five years later, Phelps showed one part of the brain was especially important—the retrosplenial cortex (RSC), which is involved in spatial memory. If males have fewer vasopressin receptors in the RSC, they were more likely to wander outside their own territories, away from their female partners, and into the domains of other vole couples.

Now, Phelps’ group, including graduate student Mariam Okhovat, have shown that these variations in brain and behaviour are driven by very subtle genetic differences. They found that the gene for the vasopressin receptor comes in two distinctive versions, which lead to either high or low levels of the receptor in the brain’s RSC. These “high” and “low” versions of the gene differ by just four mutations, which are inherited as a stable quartet.

All of this makes for a remarkably coherent story. You have two versions of the vasopressin receptor gene—a “high” one that produces more receptors in the RSC, and a “low” one that produces fewer. We know that vasopressin is released during social and sexual encounters, and that the RSC is involved in spatial memory. So it stands to reason that the levels of vasopressin receptors in this critical region affects a vole’s ability to remember the locations of social encounters—whether fights with rival males, or liaisons with alternative females.

Males with the “high” version of the gene have lots of vasopressin receptors in their RSCs. They remember social encounters very well, spend more time at home, and are more faithful to their partners.

By contrast, males with the “low” version of the gene have fewer vasopressin receptors in their RSCs. “We think that they have a poorer ability to remember the location of social encounters, so they keep coming around more,” says Phelps. They intrude into the territories of other males more often, encounter more females, and have more sex outside their usual relationships. But they’re also poorer at guarding their own mates. Their wanderlust makes them more likely to cuckold and to be cuckolded.

The critical thing is that both of these strategies “work”. The “high” males who stay are home sire more pups with their chosen partners. The “low” ones who wander around sire more pups with other females. Both are valid strategies, and their relative merits probably depend on how big the prairie vole populations are. If they’re booming, there are plenty of females around, and wandering males may have an easier time. If populations are small, the stay-at-home males might do better. This probably explains why natural selection has kept both the high and low versions of the vasopressin receptor gene around.

To Phelps, the weakest part of this story is the link between vasopressin receptor levels in the RSC and memory. “There’s always a question mark at the psychological level: how changes in the brain produce changes in the field behaviour,” he says. “We don’t really know and we only have good guesses.”

He’s now planning to inactivate that particular part of the brain before putting voles through laboratory tasks and watching their behaviour in natural settings. That will tell him what kind of behavioural differences to look out for. Then, he hopes to edit the voles’ DNA—specifically those four mutations that distinguish the “high” and “low” versions of the vasopressin receptor gene—to see if that changes their behaviour.