Scientists Tickle Rats and Discover Brain’s ‘Play Spot’

How important is play to an animal like a rat? It could be as essential as taking a breath. When scientists removed rats’ cerebral cortex, the brain area that governs higher cognition, the animals still engaged in mock fighting—a behavior known to be associated with play in rodents.

So researchers at the Bernstein Center for Computational Neuroscience Berlin set out on a hunt underneath the cerebral cortex to find a control center for play in a new study published on Friday in Neuron. By tickling rats, an activity many of the animals have been shown to respond positively to, and observing their play fighting, the team identified a spot within the brain stem called the periaqueductal gray (PAG)—the most primitive part of the brain and one that controls breathing and modulates pain. This tunnel-like structure acts as a two-way relay that shuffles information between the brain stem and the prefrontal cortex. Shutting off the PAG caused the rats to sharply reduce vocalization and play, both with humans and with fellow rats.

“We figure that play has been around for a long time because a lot of species of animals do it. It’s something that’s quite [evolutionarily] conserved,” says lead study author Natalie Gloveli, a graduate student at Humboldt University of Berlin.

Gloveli adds that past research has found many other brain regions that modulate and shift play behavior rats partake in, such as pinning and pouncing. But her team’s new findings suggest that the PAG, and specifically its lateral columns, is required for play and ticklishness.

Scientists have previously shown that rats will still engage in playful behavior even without a brain cortex, which is the organ’s outermost layer and is associated with higher-level processes, including memory, language and thought. To find the specific neuronal structures associated with play, Gloveli and her colleagues decided to focus on the midbrain. Sergio Pellis, a neuroscientist at the University of Lethbridge in Alberta, was surprised by the findings.

“My expectation was that the PAG would be interesting but not that interesting,” says Pellis, who was not involved in the recent study. “Clearly it is doing more than just relaying information.”

The PAG has a wide range of known functions in various animals, Pellis says. For instance, it is significantly involved in regulating pain and fight-or-flight behavior. Discerning whether play is also a fundamental survival response is difficult, however, Gloveli notes.

“It’s a super interesting concept to think about because we all know from personal experience how much play is instinctive to humans,” she says. Studies have shown that playing is central to a child’s health, for example.

Studies on play in the brain used to be much trickier. Scientists would use an implanted electrode and accompanying wire on juvenile rats—but while they played, their scampering would disrupt brain activity recordings. For the new study, the team drugged the rats with muscimol and lidocaine, which inhibit the targeted region of the PAG. The researchers then recorded the relevant neuronal activity before, during and after tickling the rats with a probe attached to the animals’ head. When the PAG was inactive, the rats largely ceased their wrestling and squeaking. The results suggest this PAG region could be crucial to play. But, Gloveli adds, “we’re not saying that the PAG is where play starts and ends. It’s involved in a circuit of other brain regions and projections.”

The study used only male rats, which was an important limitation, says Margaret McCarthy, a neuroscientist at the University of Maryland School of Medicine, who was not involved in the research. She hopes follow-up studies will include female rats, which are known to have different rates of play and ways they like to engage in the activity.

While McCarthy and Pellis say this study is a significant step forward, they add that scientists are unsure how the research might translate from rodents to humans. Play is also a murky concept and ambiguous to measure, with some experts debating that it is hard to define in other animals.

“We can’t ask the rat, ‘Are you laughing? Does this feel like tickling? Does this feel good?’ We have to infer it from the things that we know, like that they make those vocalizations when they’re happy, and they don’t make them when they’re not happy,” McCarthy says.

Even if emotional states in animals are hard to distinguish, Pellis says that following their behavior and closely observing what’s happening in their brain can lead to “amazing” findings that can get researchers closer to the basis of play.