Ultrasound pulses to the brain send mice into a state of hibernation

The experiments offer an intriguing clue to technology that may induce torpor in humans in the future.

For many animals, life is a cycle of scarcity and plenty. Hibernating creatures cower underground in winter, slowing down their metabolism so they can arrive in spring without food. Even laboratory mice, if starved of food, can enter a state called torpor, a sort of sleep mode that saves energy.

C' is something humans have long fantasized about ourselves: If we ever leave this planet and travel to space, we will experience our own period of scarcity. Science fiction writers tend to imagine mysterious technology that keeps humans in stasis, able to survive centuries of silence before emerging into a new life. For now, it's a technology that's out of reach.

But as scientists strive to understand states like torpor and hibernation , tantalizing details of how the brain controls metabolism have emerged. Researchers reported Thursday in the journal Nature Metabolism that they were able to send mice into a state of torpor by targeting a specific part of the brain with short bursts of ultrasound. It's unclear exactly why ultrasound has this effect, but the results suggest that studying the neural circuits involved in torpor may reveal ways to manipulate metabolism beyond the laboratory.

Ultrasound devices, which generate high-frequency sound waves, are best known for their imaging powers. But they have also been used by neuroscientists to stimulate neurons. Properly tuned, sound waves can travel deep into the brain, said Hong Chen, a professor of biomedical engineering at Washington University in St. Louis and author of the new paper. In 2014, William Tyler, now at the University of Alabama at Birmingham, and his colleagues applied ultrasound to a sensory region of the brain and found it improved a subject's sense of touch. A growing body of work is exploring ultrasound as a treatment for disorders like depression and anxiety.

Curious to know more about a region of the brain that regulates temperature body in rodents, Dr. Chen and his colleagues built tiny ultrasonic mouse caps. The devices trained six bursts, each consisting of 10 seconds of ultrasound, on the selected area of ​​the rodent's brain. (Researchers studying the brain with ultrasound must carefully adjust their devices to avoid heat that can damage tissue).

Mice, the researchers noted, have stopped moving. Measurements of their body temperature, heart rate and metabolism showed a pronounced drop. The mice remained in this state for about an hour after the ultrasound bursts, then returned to normal.

A closer look at the neurons involved in this answer, the researchers identified a protein in their brain membranes, TRPM2, which appears sensitive to ultrasound; when the researchers reduced protein levels in the mice, the mice became resistant to the effects of ultrasound.

This is an important step in understanding how ultrasound affects neurons, said Davide Folloni, a researcher at the Icahn School of Medicine at Mount Sinai in New York who studies the brain using ultrasound; the details have been largely elusive.

But it's also possible that the heat generated by the ultrasound, and not just the ultrasound itself, affects TRPM2 in the brains of mouse, a point that was raised by Masashi Yanagisawa and Takeshi Sakurai of the University of Tsukuba in Japan, in separate interviews. The two studied neurons in this region of the brain and their link to states of torpor. Both may be at play, Dr. Chen said.

In one of the most tantalizing parts of the study, the researchers checked whether the animals that do not usually experience torpor — rats — behaved differently when the brain region was stimulated with ultrasound. Indeed, they seemed to slow down and their body temperature dropped.