Long-term memories survive even when the brain temporarily loses more than half of its synaptic connections during artificial hibernation, according to a study published on August 13 in Science. Researchers found that preserved higher-order architectural patterns in neural connectivity, rather than individual sturdy synapses, enable accurate recall following major neural remodeling.
A fundamental dogma of neuroscience holds that memories are forged when individual connections between neurons grow stronger through a process known as long-term potentiation. For decades, researchers believed synaptic potentiation to be the key to long-term memory retention. An old adage in the field summarizes the mechanism: Neurons that fire together, wire together.
However, a collaborative research team including scientists from the Okinawa Institute of Science and Technology (OIST), the University of Tsukuba, the Exploratory Research Center on Life and Living Systems, and the National Institutes of Physiological Sciences has challenged that long-held view. Their findings indicate that memory stability relies instead on resilient patterns of neural architecture.
Artificial Hibernation and Rapid Brain Remodeling in Mice
To investigate how memories persist despite extensive physical changes in the brain, researchers turned to an experimental model involving artificial hibernation. Natural hibernation enables creatures to survive harsh winter conditions through decreased metabolism and dramatically reduced brain activity, while still retaining memories formed beforehand.
In 2020, a team led by Takeshi Sakurai at the International Institute for Integrative Sleep Medicine, Tsukuba Institute for Advanced Research, and the University of Tsukuba induced artificial hibernation for the first time in mice by switching on a specialized set of brain neurons. For the recent study, researchers subjected lab mice to experiments that imparted new memories, such as associating a specific setting with a mild paw shock or learning the locations of sugar pellets in a maze. Following training, the mice were pushed into artificial hibernation for two days.
The physical transformation of the brain occurred rapidly. Within 30 minutes, brain tissue began paring down synapses, and within 24 hours, over half of the synaptic connections had vanished. Despite this massive structural loss, the mice retained their pre-hibernation memories.
Engram Architecture Versus Individual Synaptic Strength
The study, published in the journal Livescience under the title Artificial hibernation reveals synaptic engram architecture associated with memory retention,
zeroes in on the hippocampus, a major memory processing hub for episodic memories.
“Previously, synaptic strengthening was thought to be key to memory recall, and that stronger synapses with larger dendritic spines were fundamental to long-term memory retention. Here, we show that not every synapse matters, and demonstrate instead the vital importance of engram architecture. The study indicates that small clusters of engram-engram synapses are preserved to enable accurate recall even after hibernation.”
Kazumasa Tanaka, research lead and head of OIST’s Memory Research Unit
While long-term potentiation remains vital for forging new memories, holding onto those memories over extended periods depends on broader network topology. As Tanaka noted, physical memory traces drift over time within days, meaning original LTP-strengthened connections can be lost while the memory itself persists.
Resilient Architectural Motifs as a Core Memory Trace
Rather than relying on a strict and consistent set of connections between specific neurons, specific clusters of connected synapses remain protected during widespread hibernation-associated brain remodeling. These preserved structural motifs act as a core memory trace,
giving the brain a mechanism to rebuild functional neural networks following major disruptions.
The structural underpinning of memory has been one of the most fundamental topics in neuroscience for decades,
the study’s authors wrote, noting that the newly demonstrated importance of higher-order synaptic architecture reshapes how researchers view the physical basis of information storage in brains.
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