How Long-Term Memories Survive Even When Brain Connections Disappear

A study of mice placed into artificial hibernation suggests that long-term memories may persist for a different reason than scientists once believed.

Researchers found that memories do not necessarily depend on preserving the same strong connections between individual neurons. Instead, broader patterns of connectivity — including clusters and network hubs — may help the brain retain memories even after many individual synapses disappear.

The findings, published in Science, offer new insight into how the brain stores long-term memories and why memory traces can remain stable despite ongoing changes in neural connections.

“This topological architecture of the broader network appears to be more important” than individual strong connections, said study co-author Kazumasa Tanaka, director of the Memory Research Unit at the Okinawa Institute of Science and Technology.

Why hibernation can reveal how memory works

Tanaka and his colleagues used artificial hibernation to investigate how memories remain intact while the brain undergoes major physical changes.

Previous research on hibernating animals has shown that extended periods of reduced metabolism can cause the brain to shrink and reduce the number of connections between neurons. Brain activity also slows considerably. Scientists have generally viewed this loss of connectivity as part of the brain’s energy-saving response.

Yet hibernating animals can retain memories formed before entering this state. Alpine marmots (Marmota marmota) and European ground squirrels (Spermophilus citellus), for example, have been reported to remember other members of their species, familiar locations and food sources after hibernation.

“Some studies have reported that their memory remains intact, allowing them to recall conspecifics, even afterward,” Tanaka told Live Science.

This raised a central question: How can memories survive when many of the physical connections between brain cells are removed?

Do strong connections between neurons store memories?

A long-standing idea in neuroscience is that memories form when connections between neurons become stronger. This process, known as long-term potentiation, or LTP, increases the strength of communication between frequently active neurons.

During LTP, neurons that repeatedly send chemical signals to neighboring cells begin transmitting stronger signals. The receiving neurons become more sensitive by increasing the number of receptors and enlarging their dendritic spines — small structures that receive input from other neurons.

These changes can create a powerful connection, or synapse, between two neurons. The concept is often summarized by the phrase: “Neurons that fire together wire together.”

Tanaka said the new research does not disprove the LTP theory. Numerous studies indicate that LTP is important for forming new memories. However, the process that creates a memory may not be the same process that preserves it over long periods.

Recent research suggests that memory traces are dynamic rather than fixed. The specific connections associated with a memory can change or “drift” over time, sometimes within days, while the memory itself remains accessible.

The researchers wanted to understand how this could happen.

Artificial hibernation caused widespread synapse loss

The study focused on the hippocampus, a brain region that plays a central role in learning and memory. The researchers examined episodic memories — memories linked to particular events, experiences or locations.

In one experiment, mice learned to associate a specific environment with a mild shock. In another, the animals learned where to find a sugar pellet in a maze.

After learning these tasks, the mice were placed into artificial hibernation for two days. The researchers observed rapid physical changes in the animals’ brains.

“We knew there would be some remodeling, but the extent of it was much greater than we expected,” Tanaka said.

Within about 30 minutes, the mice had begun losing synapses. After 24 hours, more than half of the synapses in some areas had disappeared.

Mice retained memories despite major brain changes

Despite this dramatic synapse loss, the mice continued to remember what they had learned before artificial hibernation.

When the animals were returned to the environment associated with the mild shock, they froze as they had before. In the maze, they also navigated toward the sugar pellet normally. Their behavior indicated that both memories had survived.

“Even if we compare animals with and without hibernation, there is no difference in their behavior,” Tanaka said.

To determine what protected the memories, the researchers compared the hibernating mice with animals that experienced long-term anesthesia and received molecules designed to block synaptic strengthening.

Both groups lost large numbers of synapses. However, the anesthetized mice no longer retained the memories, while the hibernating mice did. This suggested that the organization of the remaining connections, rather than simply the number or strength of individual synapses, was critical.

Memory hubs and synapse clusters may preserve memories

When the researchers examined the brains of the hibernating mice more closely, they found that some groups of synapses were unusually resilient.

These surviving connections tended to form two types of structures. The first involved network hubs, where one neuron sent signals to several neighboring cells. The second consisted of clustered dendritic spines, where multiple structures receiving signals were positioned close together and connected to different neurons.

Together, these arrangements created a broader “topological” pattern associated with the memory. The researchers found that these structures were less likely to be eliminated during artificial hibernation.

“Its unique structure is preserved during hibernation. We found that it was completely destroyed under anesthesia,” Tanaka said.

The size of individual dendritic spines did not appear to determine whether a connection survived. Instead, the researchers believe that the way the connections were grouped and positioned may be more important for long-term memory retention.

What the findings mean for the future of memory research

The study provides evidence that physical memory traces in the brain can change substantially without erasing the memories they represent. It also suggests that memory storage may depend on the architecture of an entire neural network, rather than a small number of permanently strengthened synapses.

More research is needed to understand how these synapse clusters form and how the brain protects them while removing other connections. The researchers are now investigating the molecular properties of these structures and whether manipulating them can alter memory retention.

The findings could eventually have applications beyond neuroscience. A better understanding of how biological networks preserve information despite change may help engineers develop more resilient data-storage systems.

For now, the research adds to growing evidence that memory is flexible and constantly changing. The brain may preserve the overall pattern of a memory even as individual neural connections are replaced or removed.

“With this study, we have just opened a new door to address this problem,” Tanaka said.