Blocking the activity of certain cells reduces play behavior in rats.

Rats are extremely playful creatures. They love playing chase and they literally jump for joy when tickled. Central to this playfulness, a new study finds, are nerve cells in a specific region of the brain.

Neurons in the periaqueductal gray, or PAG, are active in rats during different kinds of play, scientists report July 28 in Neuron. Blocking the activity of those neurons makes the rodents much less playful.

The results give insight into a poorly understood behavior, particularly in terms of how play is controlled in the brain.

When scientists tickled lab rats (one shown) and played a game with them, nerve cells in a brain region called the PAG became active. The team suspects that this region controls playfulness.“There are prejudices that it’s childish and not important, but play is an underrated behavior,” says Michael Brecht, a neuroscientist at Humboldt University of Berlin.

Scientists think play helps animals develop resilience. Some researchers even relate the behavior to optimal functioning, For people, “When you’re playing, you’re being your most creative, thoughtful, interactive self)” says Jeffrey Burgdorf, a neuroscientist at Northwestern University in Evanston, Ill., who was not involved in the study. This is the opposite of some depressive states, and Burgdorf’s own research aims to turn understanding of the neuroscience of play into new therapies for mood disorders. In the study, Brecht and colleagues got lab rats used to being tickled and played with in a game of chase-the-hand.

Rats play, they squeal at a frequency of 50 kilohertz, which humans can’t hear. The researchers recorded these ultra-sonic giggles as a way of measuring when the rats were having “fun.”

Brecht and colleagues suspected the PAG—which is involved in many instinctual responses and automatic functions, such as controlling breathing and pain — might be involved in play behavior. That’s partly because of the PAG’s role in controlling vocalizations, which help coordinate play. If your playmate stops laughing, it is time to stop play-fighting.

The team recorded activity from individual cells in the PAG while rats played chase-the-hand or were tickled. Columns of cells in the PAG were active during play, the researchers found. “These cells really go crazy, especially in response to tickling,” Brecht says.

Importantly, the same cells were active during both chasing and tickling. “This was where we thought: These are the cells,” Brecht says. “They’re not about moving, or touch. They’re about fun.” Making the rats anxious by putting them on an elevated, brightly lit platform suppressed playfulness and giggles, and reduced activity in these “fun” cells.

The team then genetically altered the cells so that their activity could be controlled using light. Blocking activity in just these cells caused the rats to play less and become less ticklish, as shown by an absence of giggles. The findings suggest that the PAG is required for play, probably as part of a neural circuit, the team says. Brecht and colleagues have previously found play-responsive neurons in the somatosensory cortex, a brain region responsible for perceiving touch.

However, other research has shown that animals without a somatosensory cortex still play. Brecht doesn’t think the same will be true for animals lacking the play-associated part of the PAG. “We think it’s a control structure for playful-ness,” he says.

Improving the understanding of this circuitry may help researchers improve their knowledge of depression in people (SN: 2/11/23, p. 18). “The people that really, really need help are the ones that can’t play,” Burgdorf says. The new study is a step toward understanding what such depressive states look like in the brain, which could one day help clinicians choose the best treatments for different patients, he says.

The team plans to study the PAG in other animals to see how it might differ across species and to see if it helps explain why some animals are more playful than others, Brecht says. One of the first things he did after realizing the region’s importance in rats was to look at the PAG in humans.

“And guess what? It’s very large,” Brecht says. “That’s not a coincidence: No animal plays as many games as we do”

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