A study conducted on sleeping mice suggests that our memories can persist even when half of the brain connections storing them are destroyed. This “remarkable” discovery sheds new light on how memory works and could one day pave the way for methods to enhance it. The findings were published in the journal Science.
“Memories may be harder to erase than we previously thought,” says Steve Ramirez of Boston University, who was not involved in the study. “This certainly significantly expands our understanding of how memory functions.”
When we encounter a stimulus, neurons in our sensory organs—such as the eyes—transmit electrical signals to the brain. Neurons then process this information by sending electrical signals to one another via connections known as synapses.
These neurons, known as engram neurons, encode information into a memory by forming new synapses and strengthening existing ones. Recalling a memory further reinforces these connections and the memory itself.
Many scientists believe that a memory persists as long as the specific synaptic structure on the engram neurons encoding that memory remains intact. This view is partly based on experiments using drugs or genetic tools to disrupt synapses on engram neurons, notes Kazumasa Tanaka of the Okinawa Institute of Science and Technology in Japan.
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However, recent studies indicate that memories persist even when the arrangement or number of these synapses changes. This has challenged our understanding of what is “necessary and sufficient” for memory retention. To address this issue, Tanaka and his colleagues drew inspiration from hibernating animals. “During hibernation, brain activity appears to drop significantly,” he says. “However, studies of animals that hibernate naturally show that upon waking in the spring, they somehow remember their conspecifics and the locations where they hid food before hibernating.”
By studying how memory is preserved during hibernation—a state in which the brain undergoes significant changes—the researchers hoped to uncover the fundamental principles by which mammalian brains store long-term memories. “Researchers are taking a very skillful and creative approach to the question of memory, using hibernation as a way to manipulate the brain,” says Ramirez.
They administered mild electric shocks to the paws of mice—which do not naturally hibernate—while the animals were in a chamber scented with alcohol, thereby creating a fear memory associated with that odor. The following day, the mice froze in fear when placed back in the same chamber, even without receiving any shocks.
The researchers then artificially induced a hibernation-like state in about half of the mice for two days. This was achieved by injecting them with metabolism-slowing drugs and placing them in a dark chamber. Five days later, the mice that had undergone artificial hibernation still froze when placed in the alcohol-scented chamber. This occurred despite brain scans revealing that more than half of the synapses on engram neurons in their hippocampi—a brain region crucial for memory—had disappeared during hibernation. “Despite the massive brain remodeling that occurs during hibernation, the memories remained intact,” says Tanaka. Dragoi says these results are relevant to humans as well, since previous studies have shown that our brains store information in a way very similar to mouse brains. “This tells us something about how our mammalian brains might work,” says Ramirez.
The team also discovered that synapses persisted in the brains of hibernating rodents, clustering tightly on the surface of engram neurons, while synapses outside these groups disappeared. This suggests that these clustered synapses are crucial for memory retention in the brain, says Tanaka.
Non-clustered synapses lost during hibernation reappeared within a day of the animals waking up; this indicates that while clustered engram synapses are essential for preserving information within memories, non-clustered synapses may be important for accessing those memories, he says.
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“This study is a remarkable step forward, as it solves a long-standing mystery in memory research: how the brain stores long-term memories,” says Priyank. …and Rao-Ruiz from Vrije Universiteit Amsterdam in the Netherlands.
The team is studying the molecular pathways through which clustered engram synapses store information and plans to delve deeper into how non-clustered synapses re-emerge, says Tanaka.
Targeting these pathways with drugs could even reveal ways to prevent or slow memory decline, says Ramirez. “This offers hope that even in cases where information seems lost to the brain—whether due to amnesia or Alzheimer’s disease—the memory might still persist.”
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