Mice retain memories despite losing half their synapses in artificial hibernation
A new study published in Science suggests that clustered synaptic connections, rather than individual synapses, are critical for memory retention, even after a 48-hour hibernation-like state.
Researchers at the Okinawa Institute of Science and Technology Graduate University in Japan have demonstrated that mice can retain their memories even after losing more than half of their synapses during an artificial hibernation-like state. The study, published in Science, challenges the prevailing hypothesis that memory relies on the physical strengthening of individual synaptic connections, which are known to be plastic and change significantly over time.
The team, led by neuroscientist Kazumasa Tanaka, utilised a technique developed in 2020 by collaborator Takeshi Sakurai at the University of Tsukuba. By activating specific Q neurons in the hypothalamus, the researchers induced a state of hypothermia and reduced metabolism known as Q-neuron-induced hypothermia and hypometabolism, or QIH. This state reduces body temperature to approximately 20 degrees Celsius and significantly decreases heart and breathing rates, placing the mice in a metabolic state between that of bears and deep-hibernating squirrels.
During the 48-hour induced state, neuronal activity in the hippocampus dropped by about 70 per cent. Imaging techniques revealed that the hibernation eradicated more than half of the synapses in the region. Despite this significant loss, which should theoretically impair memory, the mice performed equally well on standard memory tasks, such as contextual fear conditioning and maze navigation, as non-hibernating controls.
The study found that the survival of memory was linked to the spatial arrangement of engram synapses, which are specialised connections formed during learning. While isolated engram synapses were eliminated by the hibernation process, those arranged in tight spatial clusters were preserved. Approximately 82 per cent of the synapses that vanished during hibernation reappeared at the same location on the same dendrite after arousal, suggesting a degree of structural stability in the broader neural architecture.
Further analysis showed that a third of the surviving clustered engram synapses were attached to a rare structure called a multisynaptic bouton, where one presynaptic terminal connects to multiple postsynaptic spines. The researchers noted that the clustered synapses were not necessarily larger or stronger than their neighbours, indicating that the specific architecture of the cluster, rather than the magnitude of individual connections, may be key to memory retention.
The team also observed that brief artificial hibernation completely suppressed the development of epilepsy in a mouse model, suggesting the brain may return to a default network state after arousal. However, Tanaka cautioned that the current findings are associative rather than causal, as there is no way to selectively manipulate the clustering of engram synapses without affecting other aspects of the network. Clinical applications for humans remain distant, requiring further studies in larger animals to assess safety and efficacy.
