Putting mice into hibernation causes a major loss of synapses

The most important thing about QIH, though, is that it can be switched on and off at will. In Tanaka’s experiments the mice spent 48 hours in the hibernation-like state and then woke up. For their synapses, these 48 hours worked like Thanos’ snap. To find out how many synapses are lost during QIH, Tanaka’s team implanted tetrodes, bundles of fine electrodes, into the hippocampus of freely moving mice. These let them record individual neurons firing. They found that activity dropped by about 70 percent once hibernation set in. The brain tissues of some animals were imaged with a technique called serial block-face scanning electron microscopy before hibernation, during it, and days after returning to consciousness. It turned out the hibernation eradicated more than half of the synapses—in principle, this should erase most of the memories. “If you accept that memory traces reside in the efficacy of individual synapses, if you lose more than half of the synaptic connections, of course what you’d expect is impairment of the memory afterwards,” Tanaka says. But the team found no such impairment. Before hibernation, the mice had been trained on two standard memory tasks. One was contextual fear conditioning, in which an animal learns to associate a particular box with a mild electric shock. The second was a plus-maze task in which the mouse learns to navigate its way to a reward. Performance in both tasks depends on memories stored in the hippocampus, which the team confirmed by creating a lesion in the region after training, which caused the memories to disappear. When other mice, ones that were put into QIH, were aroused, though, they performed on these tasks just as well as the mice that did not hibernate. “What we found in these two different behavioral paradigms is the memory was completely intact,” Tanaka claims. The survival of these memories through the purge of the synapses was also confirmed by brain activity recordings. Place cells, hippocampal neurons that fire when an animal occupies a particular spot, still fired in the same locations after arousal. And a decoder that read out the population activity could reconstruct where the mouse was just as accurately as before. Tanaka thinks we should be careful in drawing conclusions about what the comparison does and doesn’t establish. “That is a major limitation of this study,” he says. “As of now, there is no way of manipulating the clustering of engram synaptic connections without compromising other aspects of the synapses and the network,” In other words, we have no way to selectively turn off these clusters to see if the memories get turned off with them. “It’s an associative study rather than a test of causality,” Tanaka warns. But if the findings hold up, it may indicate a memory doesn’t need any particular synapse to survive, as long as the broader neural architecture around it is preserved. But Tanaka’s lab is already considering a much weirder and potentially more profound implication. “If the brain rebuilds itself after hibernation, does it rebuild the state it was in beforehand, or some preferred configuration of its own?” Tanaka asks. To find out, the team induced brief artificial hibernation in mice engineered as an epilepsy model, just before seizures had developed in the animals. “We found that the development of epilepsy was completely suppressed after hibernation, even though there were no additional manipulations taking place,” Tanaka claims. This, he argues, suggests the brain after hibernation returns to a kind of default network state, something like its factory settings, rather than simply returning to where it left off. As epilepsy-related findings are still unpublished, Tanaka hopes his team will include them in a follow-up paper. Still, even if these early observations are confirmed, it’s going to be a long time before Tanaka’s findings find any clinical applications in humans. “There are so many challenges still remaining—more rigorous measures of safety, and ethics as well,” Tanaka says. “All of the studies so far have been done in mice. We need to move on to rats or monkeys and see if artificial hibernation actually has impact on the functioning of the brain or not. We still have so many things to do.” Science, 2026. DOI: 10.1126/science.aee7004