Putting mice into hibernation causes a major loss of synapses

Researchers induced a hibernation-like state in mice and found it eliminated more than half of their synapses, yet the animals appeared to retain previously formed memories, according to a study published in Science and covered by Ars Technica.

The work was led by Kazumasa Tanaka, a neuroscientist at the Okinawa Institute of Science and Technology Graduate University in Japan. The central puzzle motivating the research is a longstanding tension in neuroscience: the dominant hypothesis holds that memories are physically encoded as strengthened, enlarged connections between neurons, yet those connections are known to shift considerably over just a few days. "If you compare the arrangement of these connections on day one with the same on day four or five, it's very, very different," Tanaka told Ars Technica. To stress-test that plasticity, his team pushed the synapse loss far beyond what normal daily fluctuation produces.

Hibernation is a natural behavior in squirrels, hamsters, and bears, but the neural circuit that triggers it is conserved across mammals, including species that never hibernate in the wild, such as mice. The team exploited a technique developed in June 2020 by Takeshi Sakurai, a neuroscientist at the University of Tsukuba and a collaborator on the study, which allows researchers to artificially activate this hibernation circuit on demand by stimulating a population called Q neurons in a region of the hypothalamus. That on-demand control let the team induce the state in lab mice and then study what happened to synapses and memory afterward.

The findings complicate the standard synaptic-strength model of memory storage. Despite losing the majority of their synaptic connections during the hibernation-like state, the mice showed signs of retaining memories — suggesting either that memories can be reconstructed from a reduced synaptic scaffold, that a subset of connections is somehow protected during the process, or that the encoding mechanism is more distributed than current models assume. The study does not appear to resolve which of these explanations is correct, per Ars Technica.

The research adds to a growing body of work questioning how robustly memories are tied to the precise physical state of synapses at any given moment. If memories can survive the wholesale reorganization triggered by induced torpor, it raises the possibility that the brain has redundant or abstract encoding mechanisms that are more resilient than the synapse-by-synapse model implies. Tanaka's team's approach — using artificially induced hibernation as a tool to force dramatic, rapid synaptic change — offers a new experimental handle on questions that have been difficult to probe with subtler manipulations.