Hibernation Induces Major Synapse Loss in Mice

Neuroscientists have discovered that inducing a hibernation-like state in mice leads to a substantial loss of synapses, the connections between neurons that are believed to store memories. This finding, published in the journal Science, challenges the prevailing hypothesis that memories are stored through the strengthening and physical enlargement of these neural connections. Kazumasa Tanaka, a neuroscientist at the Okinawa Institute of Science and Technology Graduate University in Japan, explained that the arrangement of these connections changes significantly over just a few days, a phenomenon known as neural plasticity. To investigate how long-lasting memories can persist on such a dynamic substrate, Tanaka's team induced a state mimicking hibernation in mice, which resulted in the erasure of over half of their synapses. Despite this drastic alteration, the mice appeared to retain their memories, suggesting that memory storage mechanisms may be more resilient or operate differently than previously understood.

Hibernation is a natural state observed in animals like squirrels, hamsters, and bears, characterized by a significant drop in body temperature, metabolic rate, and heart rate. The neural circuitry that controls hibernation is conserved across mammals, meaning it is present even in species that do not naturally hibernate, such as mice. In June 2020, a research team, including neuroscientist Takeshi Sakurai from the University of Tsukuba and a collaborator on Tanaka's study, developed a method to artificially activate this hibernation circuit in mice. This activation is achieved by stimulating a specific group of neurons, known as Q neurons, located in the hypothalamus, a region of the brain crucial for regulating various bodily functions, including temperature and metabolism.

The research involved artificially triggering the hibernation circuit in mice, leading to a state where their physiological functions were significantly suppressed, akin to natural hibernation. Following this induced state, the researchers observed a dramatic reduction in the number of synapses. Synapses are the junctions between neurons where information is transmitted, and their density and strength are considered key indicators of learning and memory. The loss of more than 50% of these connections in the hibernating mice was a significant observation, as it directly contradicted the established theories of memory consolidation, which posit that memories are encoded by stable or strengthened synaptic connections.

The retention of memories by the mice after such a profound synaptic loss raises critical questions about the nature of memory storage. It suggests that either the memories are not solely dependent on the physical integrity of individual synapses, or that the brain possesses mechanisms to rapidly re-establish or compensate for lost connections without erasing the stored information. This discovery opens new avenues for research into memory formation, preservation, and potential therapeutic strategies for memory-related disorders. Further investigation is needed to understand the precise mechanisms by which memories are maintained in the face of such extensive synaptic turnover and to explore the implications of these findings for human cognition and neurological health.