Our leading hypothesis for how our memories are stored is that when you learn something, the connections among neurons involved get stronger and physically larger, and that constitutes the memory. The trouble is that these connections significantly change over time—they’re plastic.
“If you compare the arrangement of these connections on day one with the same on day four or five, it’s very, very different,” says Kazumasa Tanaka, a neuroscientist at the Okinawa Institute of Science and Technology Graduate University in Japan. To learn how a memory that can last for years can sit on hardware that shifts every few days, Tanaka’s team made the shift a bit more dramatic. In a recent Science study, they induced a hibernation-like state in mice, which basically erased the state of more than half of their synapses. And yet the mice apparently have kept their memories.
Hibernation on demand
Hibernation is a specialty of squirrels, hamsters, and bears, but the neural circuit that triggers it is conserved across mammals, and is present in species that never hibernate in the wild—like mice. In June 2020, a team of researchers led by Takeshi Sakurai, a neuroscientist at the University of Tsukuba and a collaborator on Tanaka’s study, developed a technique to artificially activate this hibernation circuit. This can be done by activating a population called Q neurons in a region of the hypothalamus.
The result is a state dubbed QIH, for Q-neuron-induced hypothermia and hypometabolism.
“With our protocol, we can bring mice’s body temperature down to somewhere around 20° Celsius, and their heart rate and breathing rate decrease significantly as well,” Tanaka explains. Whether that counts as real hibernation depends on which hibernator serves as a reference. Bears in a hibernation state reduce their metabolic demand but don’t change their body temperature, which remains around 36° or 37° Celsius. On the other extreme, some species of squirrels enter super deep hibernation where their body temperature can go very close to freezing. “Artificial hibernation sits somewhere in the middle of that spectrum,” Tanaka says.
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.
Synaptic purge
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.
Returning synapses
Watching the same dendrites over eight days revealed that the synapses that vanished during hibernation reappeared after arousal and 82 percent of them came back at the same spot on the same dendrite they had occupied before, far above what chance would produce.
The synapses that vanished weren’t a random sample either. Scientists have developed a technique called eGRASP, which makes a connection glow green only where a neuron tagged during learning is connected to another neuron tagged during the same learning event. The team used this to look specifically at engram synapses, specialized synaptic connections between memory-storing neurons. It turned out that engram synapses sitting alone on a dendrite were eliminated by hibernation; engram synapses arranged in tight spatial clusters were preserved. Why clustering protects them is not yet understood, though. “Mechanism-wise, we don’t know,” Tanaka says. “That is one of the ongoing projects in the laboratory.”
What the team could do is look at the architecture of these clusters.
Multisynaptic boutons
Tracing the surviving clusters, Tanaka’s team found that a third of the clustered engram synapses were attached to something called a multisynaptic bouton. “Usually a single presynaptic terminal makes a synaptic connection with a single postsynaptic spine—a one-to-one relationship,” Tanaka explains. “In multisynaptic boutons, one presynaptic terminal makes synaptic connections with multiple postsynaptic spines. This is a rare structure. It’s difficult to find in the brain.”
In randomly chosen synapses from non-hibernating mice, only 3.3 percent sat on a multisynaptic bouton. The clustered engram synapses seen here were, if anything, slightly smaller than their neighbors—they weren’t the enlarged, strengthened connections the classic model would predict.
To check that this pattern really tracked memory rather than a general pattern of synapse loss, the team ran a negative control: they put a group of mice through long-term anesthesia combined with cytochalasin D, a drug that blocks the enlargement and stabilization of synaptic connections. That combination, just like QIH, suppressed neuronal firing and stripped out a comparable share of synapses, but the mice came out of it with impaired fear memory. In those animals, the clustered engram synapses were destroyed indiscriminately—just like every other synapse.
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.
Factory settings
“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
Jacek KrywkoAssociate Writer
Jacek KrywkoAssociate Writer
Jacek Krywko is a freelance science and technology writer who covers space exploration, artificial intelligence research, computer science, and all sorts of engineering wizardry.
Source: arstechnica.com
