A laboratory animal’s environment can have a dramatic impact on its behavior. For example, rats reared in enriched housing and large social groups are adept at coping with stress. Rodents living in conventional cages, however, commonly show signs of depression and display repetitive behaviors.
But aside from studying rodents in the wild, researchers have limited options for probing natural rodent behaviors, says Peter Kind, professor of neuroscience at the University of Edinburgh.
“We’re fed up with using very specific tasks to ask animals the questions we have about their cognitive abilities,” Kind says. “We really want to have an environment where the animals could just tell us.”
So Kind and his colleagues designed a large, multistory playpen that they refer to as the “Habitat.” Approximately 26 times larger in volume than a standard rodent cage, the Habitat consists of 16 smaller interconnected units that together can comfortably accommodate 30 rats and the objects and obstacles that keep their lives interesting. (This work is part of the Simons Initiative for the Developing Brain, a project funded by the Simons Foundation, The Transmitter’s parent organization.)
That modular structure enables the researchers to easily manipulate the animals’ environment. By adding a tunnel-like piece that connects distant modules, for instance, Kind’s team can alter routes between the chambers to test spatial memory in autism rat models.
The Habitat’s complexity increases the rats’ behavioral possibilities, says Raven Hickson, a postdoctoral research fellow in Kind’s lab. “It gives the animals more ways of expressing their preferences and fulfilling their own needs.”
Though the research is in its early stages, Hickson and her colleagues have already housed multiple rat colonies for nine-week stints. Electrodes implanted in the animals’ brains record circuit dynamics when rats are alone or surrounded by other animals, for instance, and could help unearth the pathways that control naturalistic behaviors, Kind says.
Kind and Hickson spoke with The Transmitter about some preliminary results, how they collect data from their colonies, and new features they plan to introduce to the Habitat.
This interview has been edited for length and clarity.
The Transmitter: How do you know that rats experience the Habitat differently from typical laboratory housing?
Peter Kind: For one thing, we see changes in behavior among rats living in the Habitat, compared with a standard cage. For instance, we have unpublished data suggesting that social novelty deficits seen in SYNGAP1 rat models are milder when the animals are reared in the Habitat. We also see huge changes in gene expression in the parts of the brain we’d expect to respond to environmental differences, including the prefrontal cortex and hippocampus.
TT: What other behaviors have you investigated?
Raven Hickson: We recently fitted all the rats with microchips, so we can automatically gather quantitative information about individual rats for the whole nine weeks that they’re in the Habitat. We can find out how they use the space, how active they are and who they hang out with.
PK: We can also get a measure of their circadian rhythms. But most importantly, we can use proximity data to start building a social network. That’s critical for understanding monogenic forms of neurodevelopmental conditions such as autism.
TT: Can you tell us more about how you track the rats?
RH: The radio-frequency tags are just like the kind you use to track your pets, but in the Habitat they are activated by antennae in each doorway. When they enter a new module, the tag transmits a barcode-like signal with a time stamp so that you know which rat was at a particular doorway at a certain time.
One drawback is that the barcode doesn’t indicate directionality, so you have to work backward from multiple “pings” to figure out where the rat was in the past. Then we watch videos to validate the automated system.
PK: So far, it’s working with 89 percent accuracy, and I think that we can improve on that.
TT: Do you only watch the rats to validate automated data?
RH: Watching the animals will always be necessary, because you see things that you wouldn’t otherwise know about. Then you can modify the Habitat to reveal those behaviors.
PK: For example, I once watched an animal that was desperate to get to a water bath on the other side of a rotating beam. He tried to cross the beam but kept falling off; then he looked up and saw another rat using a stationary beam. He tried one last time on the rotating beam and then moved up a level and used the fixed beam. I can’t say for sure that the animal learned vicariously, but it certainly looked like it.
If we wanted to, we could set up the Habitat to test that behavior. For example, we could use doors that open only when a rat presses a lever in a certain way, encouraging the rats to learn by observing other animals.
Also, watching the footage is fun. In Raven’s office, there’s a large screen with a live feed from the different modules, and you’ll often find a crowd of people in there.
TT: What impact do you think the Habitat could have on basic research?
PK: I think it could tell us whether some genetic models are more resistant to environmental changes than others. I’d also like to test whether the rats’ behavior in the Habitat is predictive of how they perform on standard tasks. Then we can start to understand some of the variability we see.
RH: We’re hoping that we’ll be able to explain some of this variability by looking at how a rat behaved for its whole life in the Habitat; then account for that behavior in a generalized linear model. That might help us to use the variability as another signal instead of drowning out the variability by using more and more animals.
TT: What’s next for the Habitat?
PK: We’re trying to move toward a system where the rats can self-recruit. If we want to investigate spatial memory, for example, the animals can recruit themselves to a task, and the experimenter doesn’t have to touch them. Human interactions can stress out some rats more than others, so you’re immediately dealing with another variable that is difficult to control.
RH: I’d love to incorporate clay soil so that the rats can burrow and engineer their own environment. Rats often use their burrows to mitigate social friction, and changes in the colony can affect how rats construct their burrows.
So far, we can open and close doorways, but what happens if we give the rats the substrate they need to open and close their own doorways? I’d love to see how we can give them more power to change the environment to suit themselves.
