What enlightenment can the insomniac eyeless fish bring us?

© Kuttelvaserova Stuchelova/Shutterstock

Leviathan Press:

Every day I feel that time is not enough, and when I think about sleeping, I always feel that it is a waste of time - but there is no way, we know how important sleep is to us - not sleeping? That is really not okay.

However, the protagonist of today's article provides us with a new perspective to look at sleep: If external signals change, do we no longer need a fixed length of sleep?

On the surface, sleep is an obvious and essential physiological phenomenon. It comes in long, languid, predictable waves across humans, elephants, birds, fish and beetles. It brings restoration, repair and learning. It follows ancestral rhythms that cycle deep within our cells and are guided by our planet’s motion around the star.

If it weren't for one annoying blind fish, maybe we could have believed this beautiful and simple fantasy.

The fish, Astyanax mexicanus, came to the attention of a New York University graduate student more than a decade ago. It's not new to science -- it's been a subject of fascination for decades among aquarium hobbyists and researchers who marvel at its ghostly appearance and the skin covering where its eyes should be.

But the fish's other quirks are more mysterious.

Mexican characin. © Wikipedia

In Manhattan, these fish are far from where they originated: a series of nondescript caves scattered throughout northeastern Mexico. In these caves, it's always dark, cool, quiet, and pretty boring. It's a seemingly perfect place to sleep.

So curious graduate student Erik Duboué decided to test whether the fish exhibited unusual sleep habits. Late one night in 2009, he arrived at the lab at 2 a.m. and noticed something odd about the sightless fish: They seemed to be very awake.

Upon further investigation, he discovered that despite the hypnotic atmosphere of their native environment, they hardly slept at all. In fact, he found that they only napped for about three and a half hours a day. And their sleep times seemed to be completely random and lasted only for short periods of time.

Oddly, these blind cave fish seem to have thrived on this irregular schedule for hundreds of thousands of years. “You’re looking at a perfectly healthy fish that just doesn’t need to sleep,” says Duboué, now a molecular geneticist at Florida Atlantic University.

Since then, Duboué and others have been studying the strange sleep of these awake creatures—stimulating them in the lab, waking them from occasional slumbers, and probing their DNA. Combined with studies of other animals and some strange experiments that have allowed humans to sleep in caves, scientists are uncovering new truths about sleep that have long puzzled us in our bright, regular world.

---

Throughout evolution, many animals seem to be able to survive on very little sleep.

Frigatebirds in the Galapagos Islands go on weeks-long (or even months-long) hunting trips at sea, napping for only a few minutes at a time during flight, totaling less than 40 minutes of sleep per night—less than one-tenth of their usual nightly rest.[1] Even intelligent African elephants appear to get only a few hours of sporadic sleep per night in the wild, yet they can live into their 60s or 70s and still retain amazing cognitive, social, language, and memory abilities.[2]

Frigatebirds occasionally sleep during flight, entering an "autopilot" mode. © Reddit

These extreme examples have called into question our long-held assumption that sleep is essential.

But the Mexican blind fish intrigued Dubue because their sleeplessness was so unexpected. Mexican blind fish of the same species also live outside the cave, zipping through the sunlit river. These fish are decorated to match their environment, have two fully functioning eyes, and enjoy a healthy 13 hours of sleep.

Two sides of the same species: one has completely normal eyes, while the other has almost completely lost its sight. © Nature

The differences between the two groups—those that live on the surface and those that live in caves—have made these fish the darlings of biologists: they offer a realistic way to probe evolutionary processes.[3] But scientists have previously focused on the fish’s obvious differences in appearance. This adaptation makes sense in some ways: if eyes were useless in total darkness, then there’d be no point wasting energy growing them or producing pigment.

Yet no one had noticed the fish's sleep patterns until Duboué came along. "It seemed like a reasonable idea to study sleep in a fish that has lived in darkness for, depending on your point of view, a million years," he says.

He conducted his first sleep-tracking experiment, using cameras to follow the fish's movements. But he couldn't resist checking on the fish. So he snuck into the lab in the middle of the night. He immediately saw that the cave fish weren't sleeping like surface fish.

From a scientific perspective, the beauty of blind cave fish is that they all display the same insomnia trait, even though they come from different geographic populations—from caves in Tamaulipas to caves in San Luis Potosí—with each population evolving independently in its own cave.

About 800,000 to 1 million years ago, during the Calabrian period, surface water flowed across the continent, making much of the region an interconnected habitat where fish could move around—swimming up and down waterways, in and out of caves, or basking in the water. And perhaps sleeping at night in a normal, circadian manner. But then the water receded. The caves were cut off from the main waterways, and the fish inside were trapped.

It happened again hundreds of thousands of years later, and even more recently as recently as 200,000 years ago—this time the new surface C. mexicana got trapped in the caves, where they continued to evolve, as species tend to do, over hundreds of thousands of years.

African elephants appear to get only a few hours of sporadic sleep each night in the wild. © HERD's elephant orphanage

Yet, in their long isolation in caves, this population of fish appears to be headed for the same, endless sleepless nights —providing a rare scientific insight into the evolution of sleep[4].

Scientists have found[5] that many adaptive traits—from eyelessness to insomnia—appear to arise through different genetic pathways. But both waves of cave-trapped fish showed changes in a gene for a neurotransmitter called hypocretin.

As Dubue explains, hypocretin is “a wake-up system.” In laboratory studies, they found that all species of blind Mexican cavefish indeed had an excess of cells that produced hypocretin.[6]

Hypocretin is not just effective in fish; it plays the same arousal role in a variety of animals, including humans. Disruptions in hypocretin can cause narcolepsy in humans and, where it was first discovered, in dogs.

“It’s a very interesting thing,” Duboué says, that this same system helps control sleep and wakefulness, “whether you’re a human, or a mouse, or a fish.” Even blind fish that only sleep for a few seconds every now and then.

Because sleep is usually controlled by two factors: circadian rhythm and external signals that maintain this rhythm.

---

In almost all animals, sleep is thought to be controlled by circadian rhythms, which in turn come from external signals called “zeitgebers.” Zeitgebers are powerful external cues that serve as nature’s lullaby (go to sleep) and nature’s alarm clock (time to wake up).

© NPR

It was once thought that circadian rhythms were regulated solely by sunlight, but researchers have since discovered that a variety of environmental forces can drive them: temperature, lunar cycles, and even food availability. For example, in a world without light, deep sea mussels living near deep-sea hydrothermal vents can tell time based on the tides.[7]

However, the Mexican blind fish lives in a completely silent "time cue". There are no changes in temperature or light, and even the tidal gravitational effect of the moon on its small pool is minimal. Some researchers have speculated that bats may fly in and out of the cave, excreting feces into the water at specific times after feeding, thus acting as a "time cue". But scientists have so far found no evidence that the rhythms of bats affect the sleep of fish.

Could it be the complete absence of this "time cue" that makes their circadian rhythms so out of sync with their surface-dwelling counterparts?

When Duboué and other researchers investigated, they found that the mystery of the circadian rhythm was complex.[8] Many animals that live without light have their latent circadian rhythms activated if they are exposed to regular light patterns. But these fish were different. “For some reason, they had lost their regulated rhythm,” Duboué says.

So how do these fish know when to sleep and when to wake up? He said there is still no clear answer to this question.

“We know that sleep and circadian rhythms are linked,” Duboué said. But studies of cavefish and other subterranean animals suggest that “the evolutionary forces driving circadian rhythms and sleep needs may be different from one another.”

The Somali cavefish, also known as the Andrews cavefish, has a unique biological clock that lasts 47 hours and is completely unresponsive to any light stimulation. © The Conversation

Many underground species sleep very little but still have functioning circadian clocks — including other cave fish that Duboué has studied in Laos and Thailand — even though they may have lived without light synchronization for hundreds of thousands of years. (Somalian cavefish have lost their circadian rhythms that follow light cues but have so far retained a rhythm synchronized with feeding.) Genetic studies suggest that fish species that have recently been isolated in caves are more likely to retain active circadian rhythms, even though they have fallen off a 24-hour sleep rhythm.

Although it may sound strange to separate sleep from circadian rhythms, it makes sense at some level of logic. Many organisms maintain circadian rhythms for activities such as eating and reproduction, but not necessarily for what we think of as sleep: bacteria, plants, and fungi are examples.[9][10][11]

Scientists have also found strange suppression or alteration of circadian rhythms in other organisms: honey bee larvae, Arctic reindeer, and certain species of mole rats.[12] Moreover, maintaining any system, including a circadian rhythm, requires energy, and food is often scarce in cave environments. So perhaps if circadian rhythms were not needed, they would have been consigned to the evolutionary scrap heap like the eyes of cave fish?

“We usually hear ‘trait’ and we think of morphology,” says Markus Friedrich, chair of the biology department at Wayne State University, who has studied the sleep rhythms (or lack thereof) of other cave-dwelling species . Like Darwin’s finches: Change your environment and your beak shape changes. So could the same be true for such a complex sleep behavior?

The exact evolutionary dynamics of this possibility are still being investigated. “The circadian clock is likely just one of many regulatory processes that influence sleep,” Friedrich said. Sleep, he noted, is like any other trait in an animal: “It’s a trait that can be shaped.”

---

On June 4, 1938, University of Chicago psychology professor Nathaniel Kleitman and graduate student Bruce Richardson went deep into Kentucky's Mammoth Cave, into a huge hall-like cave, to test whether being in an extreme environment without regular light would change their sleep rhythms.

© The University of Chicago Library

They brought lanterns, thermometers and mousetraps (so they wouldn’t be disturbed). But no clocks. The nearby Mammoth Cave Hotel provided beds, fine linens and meals at random times. They spent 32 days in the cave, where the temperature was a constant 54 degrees Fahrenheit (about 12 degrees Celsius) and Kleitman wrote in his 1939 book Sleep and Wakefulness, “silence, and total silence.”

During their month-long stay, the two scientists settled into a 28-hour daily cycle, sleeping for about nine hours and staying busy for the next 19. This seemed to confirm Kleitman's point that "there is no basis for proving that some cosmic force determines the 24-hour rhythm"—but it also suggested that there are inherent forces that cause humans to develop a unique, daily, rhythmic cycle of sleep.

Since then, other human cave sleep experiments have involved longer stays—taking people out of their familiar “clocks,” like Italian sociologist Maurizio Montalbini’s year-long cave stays. Montalbini has conducted numerous record-breaking cave stays, often alone, including one from 1993 that lasted 366 days (he thought it was only 219 at the time).

Montalbigny. © IALP Mountain Museums

In other studies of people who voluntarily isolated themselves underground or in super-shelters, some people developed a rhythm of 14 hours of sleep followed by 34 hours of activity, while another developed a daily cycle of up to 58 hours.[13] Overall, however, most people still maintained a close to 24-hour cycle, highlighting the role of circadian rhythms in our bodies, even in the absence of a standard timeline for a small portion of our lives.

“We learned from these experiments that we are actually very similar to fruit flies in that the circadian clock is the dominant force regulating sleep activity,” says Friedrich, who studies sleep in subterranean beetles that live in giant caves (the same caves where Kleitman and Richardson were stranded).

Friedrich notes that fruit flies actually tend to wake up before the sun rises, perhaps to prepare for the best time to forage. Similarly, humans and other animals may be influenced by predictable day-night cycles to stay awake and ready for the best time to find food. In this way, “animals are predictors of future events,” Friedrich says. But for cavefish, in an environment without these fluctuations, the future is more or less like the present: All times are equally suitable for eating, just as they are for resting or staying awake.

Early experiments in humans with “time deprivation” paved the way for powerful manipulation of sleep and other physiological functions, such as hormone release and the immune system, during the circadian cycle. Over time, the critical role of circadian rhythms in tissue biology has been increasingly recognized, and in 2017, the Nobel Prize in Physiology or Medicine was awarded to three researchers who revealed the molecular basis of the circadian cycle.

In a 2001 tribute to Kleitman, Jerome Siegel, director of the Sleep Research Center at the Los Angeles Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles, wrote that Kleitman’s cave experiments were “a pivotal event in the history of human circadian research.”[14]

© Gifer

But can this powerful force that drives us to sleep be overturned?

During the cave experiments in the 1930s, one of Kleitman’s goals, a newspaper clipping from the time wrote, was to “determine how easily man can break away from the habit of a 24-hour clock.” More than half a century later, Montalbini explained that he conducted his extended underground stays without his “time cue” in part to better understand what might happen when humans spend extended periods away from Earth’s rhythms.

It turns out that 32 days, or even 366 days, is not enough time to turn these scientists into completely irregular sleepers, and certainly didn’t take away their eyes.

So what would happen if we were to leave the comfortable rhythms of Earth's surface and move to a planet or moon with a radically different solar day, or to live for multiple generations in a space colony or underground metropolis? Would our species also deviate from the orderly eight-hour sleep pattern?

Friedrich is convinced that it will. “We are evolving to be highly adaptable,” he says, and it stands to reason that, given enough time, a new sleep pattern adapted to our new environment will become dominant.

This possibility is supported by research on how human sleep changes in response to different time cues. It has been found that a lack of hypocretin cells (the same cells that are overabundant in Mexican cavefish) leads to sleep disorders in humans, as well as narcolepsy. Siegel has long sought to better understand sleep and what factors trigger or hinder it.

“There are a lot of myths about human sleep,” Siegel says. “Even my colleagues in the sleep science field debate this.” One popular myth is that we’re meant to sleep when it’s dark and wake up when it’s bright — in 12-hour sleep cycles — and that artificial light in the industrial age disrupted that pattern.

But Siegel said that's not the case.

© Karmara

In some of his recent research, he has explored the power of time to regulate human sleep. Rather than isolating people from these factors, as he did in his cave experiments, he has sought to find people living in their most natural state, with clues from our ancestors. Siegel has spent years studying the sleep patterns of hunter-gatherers and traditional agricultural groups in Africa, South America, and the South Pacific. This work has led him to the power of an often-overlooked time cue that appears to regulate human sleep: not light, but temperature[15].

For example, his research tracked sleep in communities in Namibia, where temperatures range from zero to over 100 degrees Fahrenheit (37.8 degrees Celsius) year-round, with considerable daytime temperature variation. In classic lab-based sleep studies, such variation would be considered a confounding factor. He sees it differently. "It's not a confounding factor, it's the normal way sleep evolved," Siegel says.

He has also been involved in studies tracking sleep deprivation in wild African elephants.[16] He believes that laboratory studies, along with widespread climate manipulation, have severely weakened this ancient and important time cue, which can sometimes have a dramatic impact on human sleep.

He suggests that relatively stable day-night temperatures, as experienced by many people living in climate-controlled environments, may be an important factor in insomnia, and suggests that insomnia affects approximately 10% to 30% of the population in industrial and post-industrial societies, whereas in contemporary hunter-gatherer and agricultural communities, even those who can keep the lights on at all times, only about 1% to 2% of the population suffers from insomnia.[17]

© Giphy

Unlike cave fish, however, most humans have lived in a contemporary clock-synchronized environment—one in which some cues, such as temperature differences, have been weakened and others, such as light duration, have been disrupted—for generations. Our traditional circadian rhythms are still trying to take charge. We have no way of knowing how many generations it will take for humans to find more sleep harmony again.

Still, sleep variability and flexibility exist in most species. The Mexican cavefish, both blind and sighted, is just the most extreme example of this—dramatically different sleep behaviors within the same species. As Duboué points out, there is already a lot of variation in individual sleep patterns among humans, ranging from five to 10 hours. And a growing body of research is finding that there are natural differences in individuals’ preferred times to fall asleep and wake up.

As Duboué argues, studying how sleep behaves in all its wild, natural variation is essential to better understanding its vast potential. Much of what we know about sleep is based on studies of model organisms, which have been bred over decades to be as consistent as possible and passed down from generation to generation in highly controlled environments. So to truly understand sleep, scientists need to put on their wellies and get back to the chaos of nature.

In their study of beetles in dark and twilight areas of Mammoth Cave, Friedrich and his colleagues found that even individual beetles can adjust their sleep patterns depending on their environment, a finding that echoes decades of research in labs testing animals' sleep responses to odd patterns of light and dark.

“You could call it sleep plasticity,” Friedrich said. “We now understand that the duration and pattern of sleep is just one of many possible outcomes.”

“What I learned from this is how quickly sleep can evolve,” Dubue says. “Sleep is probably one of the fastest evolving traits.” If a Mexican carp that found itself trapped in a cave could give up regular, focused sleep (relatively) quickly, in just a few hundred thousand years, that raises the question: Does a long, uninterrupted night of sleep really matter?

As Dubuey points out, sleep doesn’t actually make sense: it’s not useful for eating, mating, or self-defense. “From an evolutionary point of view, sleep doesn’t really make a lot of sense, and yet it persists throughout the animal kingdom.” [18]

So these fish and other strange animals that don't tire easily have opened up a rather maddening Pandora's box: Do we really know what the purpose of sleep is?

In fact, theories abound, but firm answers are elusive.

We have not yet been able to read the detailed terms of the deal, Faustian or otherwise, that these tireless creatures have struck in evolution to escape the demands that seem so rigid and unquestionable to animal life.

As for Duboué himself, he will continue to ponder these questions in the quiet of the night. “I never sleep well,” he says. “I am a complete insomniac.” So he will have plenty of time to solve the next puzzle in the strange world of sleep.

References:

[1]www.nature.com/articles/ncomms12468

[2]journals.plos.org/plosone/article?id=10.1371/journal.pone.0171903

[3]onlinelibrary.wiley.com/doi/abs/10.1002/jez.b.22978

[4]www.cell.com/current-biology/fulltext/S0960-9822(11)00292-2

[5]onlinelibrary.wiley.com/doi/full/10.1111/ede.12412

[6]elifesciences.org/articles/32637

[7]www.nature.com/articles/s41467-020-17284-4

[8]www.nature.com/articles/ncomms3769

[9]www.science.org/doi/10.1126/sciadv.abe2086

[10]academic.oup.com/plcell/article/18/4/792/6114862

[11]journals.asm.org/doi/10.1128/microbiolspec.funk-0039-2016

[12]royalsocietypublishing.org/doi/10.1098/rspb.2013.0019

[13]www.frontiersin.org/articles/10.3389/fphys.2019.00442/full

[14]www.ncbi.nlm.nih.gov/pmc/articles/PMC9148915/

[15]www.cell.com/current-biology/fulltext/S0960-9822(15)01157-4

[16]journals.plos.org/plosone/article?id=10.1371/journal.pone.0171903

[17]www.nature.com/articles/s41598-019-53635-y

[18]journals.biologists.com/jeb/article/221/11/jeb159533/34132/The-origins-and-evolution-of-sleep

By Katherine Harmon Courage

Translation/Yuba and Thin Bamboo

Proofreading/tim

Original article/nautil.us/what-we-can-learn-from-an-insomniac-fish-405226/

This article is based on the Creative Commons License (BY-NC) and is published by Yuzhu and Shouzhu on Leviathan

The article only reflects the author's views and does not necessarily represent the position of Leviathan