Mice retain memories after losing half of hippocampal synapses in artificial hibernation
New research suggests memory is stored in broad network architecture rather than individual synaptic connections.
Mice can fully recover complex memories even after losing more than half of their hippocampal synapses during a state of artificial hibernation. The findings, led by Kazumasa Tanaka at the Okinawa Institute of Science and Technology, challenge the long-held belief that memory depends on the preservation of specific, strengthened individual connections.
To test the limits of memory stability, researchers induced a state called Q-neuron-induced hypothermia and hypometabolism (QIH) by activating Q neurons in the hypothalamus. This process triggered a hibernation-like state that reduced hippocampal activity by approximately 70% and eradicated over 50% of the synapses within 48 hours. Despite this massive synaptic purge, the mice showed no impairment upon awakening, fully retaining memories of maze navigation tasks and contextual fear conditioning.
The Architecture of Memory
Traditional neuroscience has largely relied on the theory of Long-Term Potentiation (LTP), which posits that memories are stored by strengthening and enlarging specific synaptic connections. However, because these connections are plastic and shift over time, scientists have struggled to explain how long-term memories persist despite constant hardware changes in the brain.
Tanaka's team discovered that the brain does not treat all synapses equally during hibernation. While isolated engram synapses were eliminated, those arranged in tight spatial clusters were preserved. Furthermore, the study found that 82% of the synapses that vanished during hibernation reappeared in the exact same spot on the same dendrite after the mice aroused.
Network Hubs and Resilience
Detailed analysis revealed a specific structural secret to this resilience: multisynaptic boutons. These are rare structures where one presynaptic terminal connects to multiple postsynaptic spines. While these boutons appear in only 3.3% of random synapses in non-hibernating mice, they were attached to a third of the clustered engram synapses that survived the hibernation process.
"If you accept that memory traces reside in the efficacy of individual synapses, if you lose more than half of the synaptic connections, of course what you’d expect is impairment of the memory afterwards," Tanaka said. He noted that the topological architecture of the broader network appears to be more important than individual strong connections.
Implications for Neuroscience
These results suggest that the brain can rebuild its physical connections without losing the information they represent, implying that memory is stored in the broader topological architecture and network hubs rather than isolated points of contact. This shift in understanding could provide new insights into brain resilience and the fundamental nature of long-term storage.
Researchers are now looking at how this "reset" of the brain's network might have broader applications. According to reporting from Ars Technica, artificial hibernation may suppress the development of epilepsy in engineered mouse models, suggesting the brain may return to a "factory settings" default network state during the process.