For six to eight months of each year, thirteen-lined ground squirrels don’t leave their small, subterranean dens. Beneath North America’s grasslands, they wait out the cold season hibernating, without any stockpile of food or source of water. They don’t eat or drink for the entire duration. Slowly, scientists are unraveling the mystery of how and why.
Specific brain regions involved in triggering thirst are strongly suppressed in hibernating ground squirrels, even during the interim periods where the rodents appear active, according to a study published November 28 in the journal Science. Combined with previous findings from the same lab group, the new research lends clarity on an extreme mammalian strategy for staying underground for so long.
In most cases, we think of thirst as a key adaptation for survival. We (and all mammals) need water for circulation, cellular function, waste removal, regulating body temperature, and more. When the concentration of ions in your blood hits a critical point, when your blood volume gets too low, or when your kidneys begin to get stressed, hormones and other signals trigger your brian to feel thirsty. You drink water, and balance is restored.
But for a brown-furred squirrel trying to live through a white winter wonderland, the impulse to leave the den and seek out water could easily be a death sentence. “It would increase the risk of predation,” says Elena Gracheva, senior study author and a professor of cellular and molecular physiology and neuroscience at Yale University. There’s the cold, of course, which is a threat on its own. Yet hungry predators prowling the surface world would likely pose this biggest risk, and be sure to pick off any ground squirrels that made the mistake of exiting the nest during the lean, winter months when prey is scarce and there’s nowhere to hide. “We don’t know for sure,” Gracheva notes, “but this is a logical explanation we’ve come to.”
Eliminating thirst thus becomes a counterintuitive way to stay alive, even when the squirrels could desperately use a drink.
Prior research from Gracheva and colleagues found that hibernating squirrels keep their blood concentrations of ions like salt at consistent levels, about equal to those of active squirrels, by seriously conserving water and sequestering ions elsewhere in the body. Hormones like oxytocin and vasopressin enable water storage and act as anti-diuretics, inhibiting urination. The brain region responsible for producing those hormones remains highly active during hibernation, despite the squirrels’ low body temperature.
Yet this physiological mechanism isn’t enough to fully explain the lack of thirst. Other signals that trigger thirst, like hormones related to kidney stress and low blood volume still circulate throughout the mammals’ bodies, which should, by all standard measures, be crying out for fluids. However, even when active during hibernation and offered water, the squirrels avoid it, per the new research.
First, some explanation: Hibernation isn’t sleep–it’s something else entirely. For weeks at a time, hibernating ground squirrels significantly decrease their metabolic rate and nearly freeze. Their body temperature plummets to between 2 and 4 degrees Celsius (35.6 and 39.2 Fahrenheit), and they exist in a sort of physiological limbo called torpor. Throughout months of hibernation, these 2-3 week periods of torpor are interspersed with one or two day bouts of arousal. Suddenly, the squirrels appear active, their body temperature rises back to normal. But still, they don’t leave the burrow and they don’t eat or drink. These active periods are thought to be important, in part, so that hibernating squirrels actually can sleep, clear waste, and maintain oxygenation of their cardiovascular system, says Gracheva.
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To determine why the squirrels don’t experience thirst or look for water during these arousal bouts, Gracheva and her co-researchers ran a bevy of behavioral and molecular experiments. First, they offered hibernating squirrels water or saline solution during periods of mid-hibernation arousal. They found that the squirrels were interested in the concentrated salt solution, but not the water. This indicated that the animals were experiencing some internal signals of their deprived state, and potentially craved salt as a way to boost their blood volume without diluting ion levels. “It’s the same principle as Gatorade,” says Madeleine Junkins, lead study author and a neurobiology researcher at Yale. If you’re severely dehydrated, you don’t want to chug plain water, as that might dilute critical ions in your body below safe levels.
Yet unlike a human athlete, the hibernating mammals drinking up their squirrel ‘Gatorade’ didn’t also seem to crave water. “We know that sodium appetite and thirst happen in different parts of the brain, and so we predicted that maybe this suppression of thirst would be associated with reduced neuron activity in [certain] brain regions,” Junkins explains.
To explore this idea further, she and her colleagues examined the squirrel brains more closely, looking at protein expression, neuron activity, and the response of isolated neurons to certain thirst-triggering hormones in a handful of squirrels over multiple tests. They found that, on their own in a petri dish, neurons from the thirst-inducing part of the brain still lit up in response to the relevant hormones (though not some other signals). There were differences in the neuron’s electrical properties, but not their response to thirst hormones. Andassessed in the context of the whole brain, the neurons’ activity was suppressed. It suggests that the neurons themselves remain capable of reacting to thirst cues during hibernation, but something is continually happening within the brain to tamp down their response. Likely, Junkins suggests, inhibitory signaling plays a role. To explore this idea further, she and her colleagues examined the squirrel brains more closely, looking at protein expression, neuron activity, and the response of isolated neurons to certain thirst-triggering hormones in a handful of squirrels over multiple tests. They found that, on their own in a petri dish, neurons from the thirst-inducing part of the brain still lit up in response to the relevant hormones (though not some other signals). But assessed in the context of the whole brain, the neurons’ activity was suppressed. It suggests that the thirst neurons themselves are relatively unchanged during hibernation, and something is continually happening within the brain to tamp down their response to thirst-inducing compounds and cues. Likely, Junkins suggests, inhibitory signaling plays a role.
Still, lots of questions remain. Ground squirrels are not well-studied, model organisms. And so their genomes and neurons aren’t well-mapped. The researchers were unable to do tests like activating or inhibiting individual neurons to see how that might shift behavior, which would be possible in a test subject like a mouse or rat, notes Gracheva. “We’re working on it, and I think in two or three years, we will be able to employ similar tools,” she says–but for now, they’re still in the dark about the specifics of the brain region they’ve homed in on.
Moreover, hibernation is poorly understood at the molecular and cellular level. Lots of behavioral research has been done, but there’s little work examining the detailed inner-functions of hibernating mammals–especially water management. “I think we are the first to actually look at [thirst during hibernation] from a physiological point of view,” Gracheva says. She and her co-researchers are also studying hunger cues and other aspects of ground squirrel’s extreme winter survival strategy–like how the animals know when it’s time to hibernate without light and temperature tells.
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In doing so, she imagines the research might one day lead to a litany of beneficial discoveries.
“We’re a curiosity-based lab,” Gracheva says. They’re not working directly on any clinical applications, and the joy of understanding animal biology is motivation enough on its own. “I feel very passionately that every animal is amazing and has something to teach us. There are so many different ways to survive in the world and so many different strategies which are fascinating,” says Junkins.
However, studying hibernation does have wide-ranging potential applications, if we can figure out how to apply lessons from squirrels to ourselves. It could improve transplant or open heart surgeries,which rely on temporary, induced hypothermia in the patients, notes Gracheva. Generally, such procedures are time–and possibility-limited because people can only safely stay in a hypothermic state for short bouts. “If we can expand this window from two to five hours, it could help save a lot of lives,” she explains. “Being in a medical school, I hear this interest in our research from real doctors.”
It may also reveal cellular or molecular targets for drugs to treat anorexia, Gracheva suggests–as they identify specific pathways for suppressing and activating hunger and thirst. And it might even help propel us into deep space.
Long-distance space travel, to Mars and beyond, is complicated by just how much humans need to consume to stay alive. If we could better control our own metabolisms and learn the secrets of eliminating uncomfortable urges in a partial hibernation state, spaceflight could carry us farther. “This is a very hot topic for NASA,” she says. From small squirrel burrows, to the vast universe, science is building unexpected bridges.
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