You’re a deer mouse, and a bird is plunging toward you. What to do? It varies.

For a mouse, survival in the wilderness often hinges on one pressing question: escape or remain still?

The optimal tactic varies depending on which mouse is being referenced. A recent study by Harvard biologists reveals that two closely related species of deer mice have developed distinctly different responses to aerial threats due to modifications in neural circuitry. One species, residing in densely vegetated habitats, instinctively seeks refuge, while a relative found in open regions remains motionless to avoid detection.

“In this instance, we successfully identified where evolution intervened to cause species from diverse environments to exhibit different reactions to the same stimulus,” stated Felix Baier, who carried out the research in Hopi Hoekstra’s lab in the Department of Organismic and Evolutionary Biology during his Ph.D. studies in the Kenneth C. Griffin Graduate School of Arts and Sciences.

“The paper illustrates that evolution can manifest anywhere, including in more central regions of the brain,” added Baier, now a postdoctoral fellow at the Max Planck Institute for Brain Research.

The results, published in the journal Nature, offer fresh insights into a group of animals that have become emblematic cases of evolutionary adjustment.

Deer mice from the genus Peromyscus comprise over 50 species inhabiting nearly every ecosystem from deserts to mountains and are the predominant mammals in North America. They serve as prime examples of adaptive radiation — a process whereby an evolutionary lineage rapidly diversifies into numerous species, each suited to specific ecological roles.

Due to extensive research conducted in the wild and in controlled settings, deer mice are often referred to as the fruit flies of mammal biology.

In the rodent evolutionary tree, deer mice diverged from the ancestors of house mice and rats approximately 25 million years ago. Interestingly, some suggest that Mickey Mouse was inspired by the Peromyscus field mice that scurried through Walt Disney’s animation studios.

The lab led by evolutionary biologist Hoekstra, the Edgerley Family Dean of the Faculty of Arts and Sciences, has devoted decades to exploring how various deer mouse species have adapted their biology and conduct. The lab has previously demonstrated how species have developed specialized traits such as fur colors, mating behaviors, and burrowing practices.

In this recent study, the researchers aimed to understand why two sister species display markedly different reactions to predators. Given that deer mice are frequently preyed upon by hawks and owls, their evasive behaviors are influenced by stringent natural selection. “It’s a matter of life and death!” exclaimed Hoekstra.

The species Peromyscus maniculatus — which inhabits densely vegetated prairies and is the most widespread of all deer mice — swiftly seeks cover upon detecting an approaching bird of prey. Conversely, the Peromyscus polionotus — which resides in open landscapes like sandy dunes or bare agricultural fields — tends to remain motionless.

To further explore these differences, the researchers placed the deer mice in an enclosure equipped with a small hideout. They set up a computer screen above the cage displaying images of small dark spots drifting against a light backdrop (simulating birds soaring overhead) and spots that suddenly expanded (mimicking predatory birds diving down).

Upon perceiving the threat of a diving bird, the prairie deer mice hastened for shelter, while the open field mice froze.

The researchers aimed to clarify the neural underpinnings of these differences. They produced a frightening sound and observed analogous reactions, indicating that the distinction was not solely due to vision or other peripheral senses, but involved central processing in the brain.

Next, they conducted immunohistochemical and electrophysiological examinations of the brains of the mice, identifying a crucial junction — an area of the brain known as the dorsal periaqueductal gray (dPAG). Activation of this region was approximately 1.5 times greater in the species that sought refuge.

Using a technique termed optogenetics, the scientists introduced proteins that function as light-sensitive ion channels into the dPAG of both species and then activated the neurons with lasers. This stimulation elicited the same responses they had observed in previous trials — even without visual stimuli.

In another trial, they inhibited activity in this region, prompting one species to behave identically to the other.

The study was executed in partnership with colleagues at KU Leuven, a research university in Belgium.

Earlier investigations by the Hoekstra lab have documented additional differences between these two species, such as mating (P. polionotus being monogamous while P. maniculatus is promiscuous) and tunneling (P. polionotus constructing long complex tunnels, whereas P. maniculatus makes brief, simple ones).

The new study provides yet another illustration of how evolution has tailored each species to its distinct environment since their lineages diverged between 1 million and 2 million years ago.

The authors hypothesize that the varied escape behaviors evolved to enhance survival prospects in their respective habitats. Deer mice in vegetated environments typically have nearby cover for safety, prompting them to flee, while those in open territories possess fewer hiding spots and only draw attention by running.

However, no species could thrive if it never took flight. The researchers discovered that the open field mice could be encouraged to flee but required a significantly greater level of threat.

Both species share the same fundamental neural framework, but evolution seems to have finely adjusted the settings to optimize each species for its specific ecology.

Hoekstra remarked that these findings resonate with a common principle in evolutionary biology: “Natural selection often fine-tunes existing neural pathways rather than completely establishing new ones,” she explained.