The Best-Laid Plans of Mice

Study shows how evolution sent deer mice scurrying down two different paths of escape

For a mouse, survival often boils down to one urgent question: flee or freeze?

But the best strategy to avoid being snatched and eaten depends on which mouse you are asking. According to a new study by Harvard biologists, two closely-related species of deer mice have evolved very different responses to aerial predators thanks to tweaks in brain circuitry. One species that dwells in densely-vegetated areas instinctively darts for cover while a cousin living in open areas goes still to avoid being spotted.

“In this case, we were able to pinpoint where evolution acted to make species from different environments have different behaviors to the same stimulus," said Felix Baier, who conducted the study in Hopi Hoekstra’s lab in the Department of Organismic and Evolutionary Biology as a PhD student in the Kenneth C. Griffin Graduate School of Arts and Sciences. Now postdoctoral fellow at the Max Planck Institute for Brain Research, Baier added: “The paper shows that evolution can act anywhere, including in more central brain regions.”

The findings [link will activate when embargo ends], published in the journal Nature, provide new insights about a group of animals that have become iconic examples of evolutionary adaptation.

Deer mice of the genus Peromyscus include more than 50 species occupying virtually every habitat from desert to mountains and they are the most abundant mammals in North America. They are prime examples of an adaptive radiation—the process by which an evolutionary lineage rapidly diversifies into multiple species, each occupying specialized ecological niches. Because they have been intensely studied in the wild and in the lab, deer mice are sometimes called the fruit flies of mammal biology.

In the rodent family tree, deer mice separated from the ancestors of house mice and rats about 25 million years ago. By some accounts, Mickey Mouse was inspired by the Peromyscus field mice that scurried through the animation studio of Walt Disney.

The lab of evolutionary biologist Hoekstra (who serves as the Edgerley Family Dean of the Faculty of Arts and Sciences) has spent decades studying how different species of deer mice have adapted their biology and behavior. In previous studies, the Hoekstra lab showed how species evolved specializations such as fur colors, mating habits, and burrowing behaviors.

In this new study, the team sought to understand why two sister species respond very differently to predators. Because deer mice are frequently hunted by hawks and owls, their escape behaviors are shaped by intense natural selection. Said Hoekstra: “It’s life or death!”

The species Peromyscus maniculatus—which lives in densely-vegetated prairies and is the most widespread of all deer mice—is quick to dash for cover after sensing the approach of a bird of prey. In contrast, the oldfield mouse Peromyscus polionotus—which lives in open areas such as sand dunes or bare farm fields—tends to freeze in place.

To better understand these differences, the investigators placed the deer mice in an enclosure furnished with a small shelter. They mounted a computer screen atop the cage and showed images of small dark dots floating on a light screen (which simulated birds soaring high overhead) and dots that suddenly loomed larger (which mimicked predatory birds diving in for the kill). When they sensed the looming threat of an approaching bird, the prairie deer mice scrambled for shelter but the open field mice froze in place.

The investigators sought to uncover the neural basis for these differences. They played a frightening sound and triggered similar reactions, revealing that the difference was not just vision or other peripheral senses, but some kind of central processing in the brain.

Next they conducted immunohistochemical and electrophysiological studies of the mice brains and located the key junction--a portion of the brain called the dorsal periaqueductal gray (dPAG). Activation of this region was about 1.5 times higher in the species that escaped.

With a technique known as optogenetics, the scientists introduced proteins that act as light-sensitive ion channels into the dPAG of both species and then stimulated the neurons with lasers. This stimulation triggered the same responses they had witnessed in the earlier experiments—even when no images were shown. In another experiment, they suppressed activity in the same region and induced one species to behave just like the other.

The study was conducted in collaboration with colleagues at KU Leuven, a research university in Belgium.

Previous studies by the Hoekstra lab have documented other differences between the same two species such as mating (P. polionotus is monogamous while P. maniculatus is promiscuous) and burrowing (P. polionotus makes long complex tunnels while P. maniculatus makes short, simple ones). The new study adds yet another example of how evolution has tailored each species to its unique environment since the two lineages separated between 1 million and 2 million years ago.

The authors theorize that the different escape responses evolved to maximize chances of survival in their respective habitats. Deer mice that live in vegetated areas usually can find cover nearby so they flee, but those that live on open ground have fewer places to hide and only attract attention by running. “You rely on your camouflage,” explained Baier. “There’s a fair chance that when you freeze, you get overlooked.”

But no species would survive if it never escaped. The scientists found that the open field mice eventually could be induced to flee, but they required twice the amount of threat.

Both species share the same basic neural machinery, but evolution apparently has adjusted the knobs to fine tune each species for its ecology. Hoekstra said those findings echoed a common theme in evolutionary biology: “Natural selection often tweaks existing neural circuits rather than constructing entirely new pathways,” she said.