Ultrasound brain pulses put mice in a hibernation-like state | Science

It’s a classic sci-fi trope: Astronauts on an interstellar journey are held in sleek, cool pods in a state of suspended animation. Although such pods remain purely fictional, scientists have pursued research into inducing a hibernation-like state in humans to lessen the damage caused by medical conditions such as heart attacks and strokes, and to reduce the stress and costs of stays future in long-distance space.

In a study published today in Nature Metabolism, scientists report that they can induce a similar condition in mice by targeting a part of their brain with pulses of ultrasound. Some experts are calling it a major technical step toward achieving this feat in humans, while others say it’s a stretch to extrapolate the results to our own species.

“It’s an amazing paper,” says Frank van Breukelen, a biologist who studies hibernation at the University of Nevada, Las Vegas and co-author of an editorial accompanying the study. The work builds on a slew of recent studies pinpointing specific populations of neurons in a region called the preoptic area (POA) of the hypothalamus. These cells act as an on-off switch for “torpor”—a sluggish, energy-saving state that animals enter when they’re cold or dangerously malnourished. In previous studies, scientists genetically engineered these neurons to respond to light or certain chemicals and found that they could cause mice to enter a torpid state even when they were warm and well-fed. Such invasive techniques can’t be easily translated to humans, however, Breukelen said. “It’s really not going to happen in humans.”

The new ultrasound study, led by bioengineer Hong Chen and her team at Washington University in St. Louis did not require genetic engineering. Chen knew from previous research that some neurons have specialized pores called TRPM2 ion channels that change shape in response to ultrasound waves, including the subset of POA cells that control rat twitching. To see what effect this had on the animals’ behavior, her team then attached miniature, speaker-like devices to the mice’s heads to focus these waves on the POA.

In response to a series of 3.2 megahertz pulses, the rodents’ body temperatures dropped by about 3°C. The mice cooled down by shifting body heat to their tails—a classic sign of torture, Bruekelen notes—and their heart rates and metabolisms slowed. By automatically delivering additional pulses of ultrasound when the animals’ body temperatures began to rise again, the researchers could keep the mice in this torpid state for up to 24 hours. When they turned off the mini-speakers, the mice returned to normal, apparently with no ill effects.

Chen’s team then repeated the experiment with 12 mice – which do not naturally go into sleep in response to cold or lack of food – and found a similar effect, although their body temperatures only dropped by 1°C in 2°C. The researchers say this suggests the technique could also work in animals that don’t normally hibernate.

Breukelen says his confidence in the team’s results is bolstered by the fact that when the researchers directed the ultrasound at other regions of the brain, the mice did not appear to enter a torpid state. This suggests that the animals’ reduced metabolism was indeed caused by stimulation of neurons in the POA, and not simply by “messing up” brain function. “I don’t think anyone wants a therapy that relies on turning off the brain and the consequences be damned,” he says. He is also encouraged that the researchers recreated the same effect in mice. Although humans do not naturally hibernate, the ability is found in species from almost every mammalian lineage, from the fat-tailed dwarf lemur of Madagascar to the Arctic ground squirrel. Perhaps humans, like mice, also have a hidden ability to enter something akin to hibernation, he says.

Others are not convinced. Shaun Morrison at Oregon Health & Science University doubts that scientists have actually observed torture in rats. Ultrasound stimulation warms the brain, he says, so it’s possible the researchers were actually activating temperature-sensitive neurons in that region, causing the animals to lower their body temperatures in response. Even if the effect is real, he’s skeptical that we’ll use ultrasound to put astronauts in suspended animation anytime soon. Human brains are much larger than mouse brains, and the POA is buried deeper, Morrison notes, making it much more difficult to target with the mini-speakers Chen and her colleagues employed. “This ultrasound technique is very unlikely to work in humans as well as in mice.”