For six to eight months of the year, thirteen lined ground squirrels do not leave their small, underground burrows. Among the grasslands of North America, they wait out the cold season in hibernation, without any supply of food or water source. They don’t eat or drink all the time. Scientists are slowly unraveling the mystery of how and why.
Specific brain regions involved in inducing thirst are strongly suppressed in hibernating ground squirrels, even during the intermediate periods when the rodents appear active, according to a study published Nov. 28 in the journal. Science. Combined with previous findings from the same laboratory group, the new research sheds light on an extreme mammalian strategy to remain underground for so long.
Thirteen lined ground squirrel. Courtesy of the Gracheva Laboratory.
In most cases, we consider thirst as an important adaptation for survival. We (and all mammals) need water for circulation, cell function, waste removal, regulating body temperature and more. When the concentration of ions in your blood reaches a critical point, when your blood volume becomes too low, or when your kidneys become stressed, hormones and other signals cause your Brian to become thirsty. You drink water and the balance is restored.
But for a brown-furred squirrel trying to navigate a white winter wonderland, the impulse to leave the den and find water could easily be a death sentence. “It would increase the risk of predation,” said Elena Gracheva, senior author of the study and professor of cellular and molecular physiology and neuroscience at Yale University. There is of course the cold, which is a threat in itself. Still, hungry predators prowling the surface world probably pose this greatest risk, and be sure to pick up any ground squirrels that have made the mistake of leaving the nest during the lean winter months, when prey is scarce and there is no place to hide. “We don’t know for sure,” Gracheva notes, “but this is a logical explanation we have arrived at.”
So eliminating thirst becomes a counterintuitive way to stay alive, even when the squirrels desperately need a drink.
Previous research by Gracheva and colleagues found that hibernating squirrels keep their blood concentrations of ions such as salt at consistent levels, roughly equal to those of active squirrels, by seriously conserving water and storing ions elsewhere in the body. Hormones such as oxytocin and vasopressin enable water storage and act as antidiuretics, inhibiting urination. The area of the brain responsible for the production of these hormones remains very active during hibernation, despite the squirrels’ low body temperature.
Yet this physiological mechanism is not sufficient to fully explain the lack of thirst. Other thirst-inducing signals, such as hormones related to kidney stress and low blood volume, are still circulating through the mammals’ bodies, which by all standard measures should be screaming for fluids. But even when they are active during hibernation and are offered water, the squirrels avoid it, new research shows.
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First some explanation: hibernation is not sleep; it is something completely different. For weeks, hibernating ground squirrels significantly lower their metabolism and nearly freeze. Their body temperatures drop to between 2 and 4 degrees Celsius (35.6 and 39.2 Fahrenheit), and they live in a kind of physiological limbo called torpor. During the months of hibernation, these 2-3 week periods of torpor alternate with periods of excitement lasting one or two days. Suddenly the squirrels appear active, their body temperature rising back to normal. Yet they do not leave the den and do not eat or drink. These active periods are thought to be important in part so that squirrels enter hibernation can sleep, clear waste and maintain oxygenation of their cardiovascular system, says Gracheva.
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To determine why the squirrels do not experience thirst or search for water during these bouts of arousal, Gracheva and her co-researchers conducted a series of behavioral and molecular experiments. First, they offered the hibernating squirrels water or a saline solution during periods of mid-hibernation arousal. They found that the squirrels were interested in the concentrated salt solution, but not in the water. This indicated that the animals were experiencing some internal cues of their deprived state, and may have been craving salt as a way to increase their blood volume without diluting ion levels. “It’s the same principle as Gatorade,” said Madeleine Junkins, lead author of the study and a neurobiology researcher at Yale. If you are severely dehydrated, you don’t want to drink plain water, as this can dilute critical ions in your body below safe levels.
Thirteen lined ground squirrel. Courtesy of the Gracheva Laboratory.
But unlike a human athlete, the hibernating mammals drinking their squirrel “Gatorade” didn’t also seem to crave water. “We know that appetite and thirst for sodium occur in different parts of the brain, so we predicted that this suppression of thirst might be associated with reduced neuron activity in the brain. [certain] brain regions,” Junkins explains.
To explore this idea further, she and her colleagues took a closer look at the squirrel brain, looking at protein expression, neuron activity, and the response of isolated neurons to certain thirst-inducing hormones in a handful of squirrels across multiple tests. They found that neurons from the thirst-inducing part of the brain, alone in a petri dish, still lit up in response to the relevant hormones (but not to some other signals). There were differences in the electrical properties of the neurons, but not in their response to thirst hormones. And when assessed in the context of the whole brain, the neurons’ activity was suppressed. It suggests that the neurons themselves remain able to respond to thirst signals during hibernation, but something is constantly happening in the brain to suppress their response. Presumably, Junkins suggests, inhibitory signaling plays a role. To explore this idea further, she and her colleagues took a closer look at the squirrel brain, looking at protein expression, neuron activity, and the response of isolated neurons to certain thirst-inducing hormones in a handful of squirrels across multiple tests. They found that neurons from the thirst-inducing part of the brain, alone in a petri dish, still lit up in response to the relevant hormones (but not to some other signals). But when 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 that something is constantly happening in the brain to suppress their response to thirst-inducing compounds and signals. Presumably, Junkins suggests, inhibitory signaling plays a role.
Yet many questions still remain. Ground squirrels are not well-studied model organisms. And so their genomes and neurons are not well mapped. The researchers were unable to perform tests such as activating or inhibiting individual neurons to see how that might change behavior, which would be possible in a subject like a mouse or rat, Gracheva notes. “We’re working on it, and I think in two or three years we’ll be able to use similar tools,” she says, but for now they’re still in the dark about the specifics of the brain region they’re working on. I went into it.
Furthermore, hibernation is poorly understood at the molecular and cellular level. Much behavioral research has been done, but little work examines the detailed inner functions of hibernating mammals, especially water management. “I think we’re the first to actually look at it [thirst during hibernation] from a physiological point of view,” says Gracheva. She and her fellow researchers are also studying hunger cues and other aspects of ground squirrels’ survival strategies in extreme winter, such as how the animals know when it’s time to hibernate without light and temperature signaling.
[ Related: Why do birds migrate? Scientists have a few major theories. ]
In doing so, she imagines that the research could one day lead to a litany of useful discoveries.
“We are a curiosity-based laboratory,” says Gracheva. They don’t work directly on clinical applications, and the joy of understanding animal biology is motivation enough in itself. “I believe 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 that are fascinating,” says Junkins.
However, studying hibernation has broad potential applications, if we can figure out how to apply the lessons of squirrels to ourselves. It could improve transplants or open-heart surgeries, which rely on temporary, induced hypothermia in patients, Gracheva notes. In general, such procedures are limited in time and capabilities, as people can only safely remain in a hypothermic state for short periods of time. “If we can extend this period from two to five hours, it could help save many lives,” she explains. “Being in medical school, I hear this interest in our research from real physicians.”
It could also reveal cellular or molecular targets for drugs to treat anorexia, Gracheva suggests, because they identify specific pathways for suppressing and activating hunger and thirst. And it could even get us into space.
Long-distance space travel, to Mars and beyond, is complicated by how much humans must consume to stay alive. If we could better control our own metabolism and learn the secrets of eliminating uncomfortable urges in partial hibernation, spaceflight could take us further. “This is a very hot topic for NASA,” she says. From tiny squirrel holes to the vast universe, science builds unexpected bridges.
