Ah, winter! Shorter days, colder temperatures, and it is so hard to get out of bed. Perhaps, like me, you sometimes envy animals who hibernate the season away. Hibernators get to eat a lot of extra food in the fall to build up body fat in anticipation of their winter slumber. Yum! Some also stash favorite foods in their dens because during periods of long hibernation they will wake briefly to relieve themselves, eat a snack and fall asleep again. Sound inviting?
Most of us associate bears with hibernation, but a variety of animals take advantage of this evolved adaptation, including certain species of primates and rodents. When they hibernate, animals experience multiple bouts of a low-metabolism state called torpor for days at a time, punctuated by occasional periods of arousal. Interestingly, mice do not have a hibernation period in winter, but enter a similar state of daily torpor to conserve energy when food is scarce.
Hibernation and daily torpor are forms of mammalian suspended animation. Both involve significant, regulated drops in body temperature, metabolism, heart rate, breathing rate, and activity, and are thought to be ways to conserve energy during food scarcity. Hibernation lasts weeks or months, while daily torpor lasts several hours a day. Physiological changes of torpor and hibernation are well studied, but little is known about how the process is regulated by the brain. A structure in the lower forebrain, hypothalamus, is thought to have a role as it controls, among other things, feeding, temperature, and sleep.
In 2020, two independent studies published in Nature identified a population of hypothalamic neurons in mice that induce the low body temperature, reduced metabolism, and inactivity characteristic of hibernation and torpor. In one study, Harvard neuroscientists looked at mice deprived of food for 10 hours and housed at cold temperatures to induce torpor. Focusing on the hypothalamus, the team used chemo-genetic tools to tag neurons naturally activated upon entry into torpor. Many of the torpor-activated neurons expressed the gene for a specific polypeptide (PACAP). Later, once the animals were fed and recovered, the team could reactivate those same neurons, sending the fed animals back into torpor.
Meanwhile, Japanese neuroscientists were investigating hypothalamus cells they call Q neurons, that produce a neuropeptide which affects feeding and activity. When they stimulated Q neurons in mice, it unexpectedly induced an extended torpor lasting several days. When they inhibited Q neurons, it impaired normal torpor. They later found that some Q neurons express PACAP and suggested these may be a subset of the neurons studied at Harvard. Whether that is the case, or these are discrete populations signaling each other to affect torpor is not yet known. Neither team saw damage to tissues and organs, or abnormalities in behavior when animals recovered from the induced state of torpor.
The neuroscientists discussed testing more species to see if these cells are preserved and if activating them can induce hibernation in non-hibernators, including humans. They speculated about uses like protecting brain tissue from injury or preserving organs for transplant. One of them spoke about a quiescent state for humans going on extended journeys into deep space. That, of course, led me back to dreaming of well-fed humans blissfully sleeping away the dark, cold, winter months.
However, until something like that is possible, I will continue to turn to my mind to survive winter and other challenges, a la Albert Camus: “In the depths of winter, I finally learned that within me there lay an invincible summer.”
Stay warm!
Post by: Nadia Fike
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Read more: 1. Hrvatin, S., Sun, S., Wilcox, O.F. et al. Neurons that regulate mouse torpor. Nature 583, 115–121 (2020). https://doi.org/10.1038/s41586-020-2387-5
2. Takahashi, T.M., Sunagawa, G.A., Soya, S. et al. A discrete neuronal circuit induces a hibernation-like state in rodents. Nature 583, 109–114 (2020). https://doi.org/10.1038/s41586-020-2163-6