Key facts
- Mice retained memories of contextual fear conditioning and a plus-maze task after an induced hibernation-like state.
- Over half of the mice's synapses were eliminated during the hibernation-like state.
- Clustered engram synapses, particularly those connected to multisynaptic boutons, were preserved.
- 82% of lost synapses reappeared in their original locations on dendrites after arousal.
- A control experiment using anesthesia and a drug blocking synaptic stabilization resulted in memory impairment.
Researchers have discovered that memories can persist even after a significant loss of synapses, challenging traditional models of memory storage. In a study published in Science, scientists induced a hibernation-like state in mice, which led to the elimination of over half of their synaptic connections. Despite this drastic purge, the mice retained memories of tasks they had learned prior to the induced hibernation.
The technique used, termed Q-neuron-induced hypothermia and hypometabolism (QIH), involved artificially activating a hibernation circuit in the mice. This lowered their body temperature to around 20° Celsius and significantly reduced metabolic rate, heart rate, and breathing rate. The effect on synapses was profound, with imaging revealing a loss of more than 50% of these neural connections.
However, when the mice were aroused after 48 hours, they performed equally well on memory tests, including contextual fear conditioning and a plus-maze task, as mice that did not undergo hibernation. Brain activity recordings, specifically of place cells in the hippocampus, also showed that the neural representations of familiar locations remained intact.
Further investigation revealed that the lost synapses were not random. While isolated engram synapses were eliminated, those arranged in tight spatial clusters were preserved. A significant portion of these clustered synapses were found to be attached to multisynaptic boutons, a rare structure where a single presynaptic terminal connects to multiple postsynaptic spines. This clustering mechanism is hypothesized to play a protective role in memory retention.
In a control experiment, mice subjected to long-term anesthesia and a drug that blocks synaptic stabilization experienced similar synapse loss but showed impaired memory. This suggests that the preservation of clustered engram synapses is crucial for memory survival, rather than just the overall reduction in synaptic connections.