Mice retain memories after losing half of hippocampal synapses

Mammalian memories may be far more durable than previously believed, persisting even after massive structural loss in the brain. Researchers at the Okinawa Institute of Science and Technology have discovered that mice can recall fearful associations despite the disappearance of more than half of the synapses within their hippocampal engram neurons.

In the study, mice were trained to associate the scent of alcohol with electric shocks. To test memory stability, the team induced an artificial hibernation state using dark chambers and metabolism-slowing drugs. Upon analysis, the researchers found that over 50% of the synapses in the hippocampus had vanished. Despite this significant loss, the mice successfully retained the memory of the fearful association. The team identified that while most synapses disappeared, small "clustered synapses" on the surface of engram neurons remained intact, serving as the critical components for retaining the memory information.

The synaptic puzzle

For decades, the prevailing scientific consensus held that long-term memories depended on the maintenance of a specific, stable pattern of synapses on engram neurons. If the physical architecture of these connections was disrupted, the memory was expected to vanish. This research drew inspiration from natural hibernators, which are known to remember social bonds and food locations after waking from deep sleep, to investigate whether the mammalian brain possesses similar resilience.

Implications for memory loss

This discovery suggests that memory storage is not dependent on a stable overall synaptic pattern, but is instead concentrated in specific, resilient clusters. This shift in understanding has significant implications for neurology and the treatment of cognitive decline. If memories are stored in these durable clusters, it suggests that information lost to amnesia or Alzheimer's disease might still physically persist within the brain, even if the pathways to access that information have been degraded.

"Memories may be harder to break than we thought," said Steve Ramirez of Boston University, commenting on the findings. Priyanka Rao-Ruiz of Vrije University Amsterdam added that the study represents a "remarkable step forward" in solving the long-standing puzzle of how the brain retains long-term information.

Future directions

While the core memory remained intact via clustered synapses, the study noted that non-clustered synapses—those wiped out during hibernation—reappeared shortly after the mice woke up. According to reports in New Scientist, this suggests that while clusters store the information, these transient synapses may be necessary for accessing those memories. Future research will likely focus on whether these access pathways can be artificially restored in humans suffering from memory impairment.