Deep sleep, brain magnets and memory

Deep non-REM sleep appears to affect how well we commit a new task to memory

Sleep specialists like to divide sleep into one of two states: rapid eye movement sleep (REM) and non-rapid eye movement sleep (non-REM). Since the discovery of REM and its tight link to dreaming in 1953, there has been a lot of research focused on this paradoxical wake-like state. But as we experience much more non-REM than REM during the night, non-REM or deep sleep might be the more important of the two states.

It’s likely there are many functions of non-REM. It could simply be a means of energy saving, reducing metabolic output during naturally selected hours of inactivity. Non-REM could involve some kind of neurological reset, allowing the neurons to replenish neurotransmitters. Perhaps the downtime is used to clear metabolites. There may be synaptic strengthening. There may be synaptic pruning. Both of these could enhance brain performance. It’s possible that non-REM performs all of these functions, and more besides.

There is an interesting experimental study on non-REM in Nature Communications this week. Researchers in Switzerland gave volunteers the task of learning a specific sequence of six finger taps, rather like asking them to learn to play a six-note ditty on the piano with the fingers of one hand but without the sound. After learning, as the subjects slept, some received a pulse of “transcranial magnetic stimulation” (TMS) directed at their motor cortex and timed to coincide with the deep, non-REM state. Although these experimental individuals didn’t notice they’d been targeted during the night and reported sleeping just as well as controls, they did less well at the six-finger memory task when tested the following day.

It’s a small study, but it does suggest that targeted TMS could be a useful experimental tool in efforts to figure out what is going on in the different stages of sleep. There is a therapeutic flip-side too. TMS is increasingly deployed for the treatment of depression and, appropriately delivered, might be able to enhance rather than disrupt non-REM sleep, thereby improving learning and memory (see this study, for instance).

In the last sentence, the words “appropriately delivered” are fairly important because I can see the growth of a poorly evidenced TMS industry, with desperate sleep-disordered people donning magnets at night and synching them with beautiful apps that promise stimulation at just the right frequency at just the right moment.

This would be about as silly as trying to run before walking. Sleep science is still in its infancy and it would seem wise to get a better handle on what is happening in our brains when we sleep before we begin self-medicating with magnets.

The horrors of sleep deprivation

The definitive demonstration of the horrors of sleep deprivation appeared in a celebrated paper published by sleep research pioneer Allan Rechtschaffen and his colleagues in Science in 1983. They used rats.

What nobody had managed until then was to design a set-up in which both experimental and control animals received exactly the same conditions but different amounts of sleep. The solution Rechtschaffen and co. came up with is as ingenious as it is disturbing.

They installed a pair of rats in neighbouring cages. In the bottom of each cage was 3cm of water, but by standing on a record-player-like disk shared by both cages the rats were able to stay high and dry. The brains of both animals were wired up to an electroencephalogram (EEG) to record patterns of wake and sleep. Cleverly, the record player was controlled by the brain waves of the experimental rat. As soon as it fell asleep, the disk began to rotate at a leisurely 3.5 rpm.

“Whenever the disk was rotated, both rats had to walk in the direction opposite to the disk rotation to avoid being forced into the water,” wrote Rechtschaffen et al. So the animals were subject to the same environment and rotation, made to walk an average of almost one mile a day, but got very different amounts of sleep. Experimental rats got almost none, whilst control rats were able to grab some rest when the experimental rats were spontaneously awake and the turntable was stationary. “This study is best viewed as a comparison between severe and moderate sleep deprivation,” they wrote.

With time, the severely sleep deprived rats began to deteriorate, showing at least two of several pathological signs, including ungroomed fur, skin lesions, swollen paws, inability to move, loss of balance and significant weakening of the EEG signal. Three of eight experimental rats died, one after just five days. When Rechtschaffen and co. carried out necropsies on the deceased they found evidence of further problems, including collapsed lung, stomach ulcers, internal bleeding, testicular atrophy, severe scrotal damage and swollen bladder. The control rats, by contrast, were in relatively good nick.

The conclusion: “Sleep does serve a vital physiological function.”

Gessner’s bear

Historia animalium by Conrad Gesner, Henry Nicholls
De urso, from Conrad Gesner’s Historia Animalium

Last month, I hosted a post by historian Florike Egmond on my Guardian blog Animal Magic, one that proved incredibly popular.

A few years ago, Egmond was in the Amsterdam University Library when she discovered an amazing collection of 16th-century drawings and watercolours of animals collected by the founding father of zoology Conrad Gessner and his fellow Swiss successor Felix Platter. These and many more illustrations feature in her new book on early modern natural history illustration, Eye For Detail (Reaktion Books, 2017) and I invited Egmond (with the kind permission of Amsterdam University Library) to put together a gallery of some of these amazing illustrations.

Inspired, I flipped through an online copy of Historia Animalium (on the brilliant website archive.org). I was able to locate many of the reproductions of many of Egmond’s originals, but I love this engraving of a bear, with its beautifully rendered fur.

Why don’t pandas have more sex?

It’s true. Male pandas have such teensy winkies that many humans trained in the ways of sexing bears have mistaken boy pandas for girl pandas. Female pandas have a reproductive window so fleeting – just a day or two a year – that even if a male panda were to erect his little soldier, it would be unlikely to see any action. Based on these two observations, many people like to imagine that pandas are sexually inadequate, a species that would surely be extinct were it not for the supportive role played by humans.

Giant panda penis, Henry Nicholls
Male or female? Reproduced from Dwight D. Davis’ 1964 monograph on the giant panda, courtesy of archive.org

The truth about pandas and sex is rather different and, in my considered opinion, a whole lot more interesting. When I meet someone who subscribes to the pandas-are-rubbish-at-sex school of thought, I have to ask how it is that this species has been roaming the earth – in roughly its current shape and form – for some 20 million years. This, I like to point out, is approximately 20 million years longer than Homo sapiens have been around.

Clearly, pandas do not have a problem with sex. In fact, from an evolutionary perspective they appear to be really rather good at it. So what is going on here? How did this myth get started and why is it still so widely held?

For all the evolutionary distance between pandas and humans, there are some superficial similarities. The panda is rounded like a human baby, it appears to have large, child-like eyes, with little or no tail and it sits on its bottom a lot, all characteristics that might account for the immense popular appeal of Ailuropoda melanoleuca. Lulled into an anthropomorphic mindset, it seems that many people see pandas as wannabe humans, quasi-hominids that would kill to have bigger penises, more frequent menstruation and much, much more sex.

The reality, in fact, is that those who mock pandas for being sexually incompetent are not really talking about actual pandas. They are referring to zoo pandas, a contrivance that says far more about the failure of humans than about black and white bears.

The first specimens to find themselves behind bars lived very short lives at Chengdu Zoo in the 1930s. They did not die because pandas are rubbish at surviving, but because they were given food fit for humans. The first panda to reach the West – a male called Su-Lin whose genitals are illustrated above – went on show at Brookfield Zoo in Chicago in 1936. The first panda conceived and born in captivity caused a stir, but only in 1963. London Zoo’s celebrity panda Chi-Chi braved the Cold War to hook up with a Soviet panda An-An at Moscow Zoo, but she died cubless in 1972. The Nixon pandas – male Hsing Hsing and female Ling Ling – spent the rest of the 1970s frustrating keepers at the National Zoo in Washington D.C. Artificial insemination and monitoring the reproductive hormones of females improved the captive panda birth stats a touch, but in March every year zoos the world over still go through the same pregnancy-based pantomime.

As far as we can tell, pandas do sex very differently in the wild. As pandas travel through their forested landscape, they leave frequent markings, olfactory messages that carry information on gender, age, proximity and fertility. When a female comes into season, these evolved signals attract males from far and wide. She may even be drawing many males together, letting them tussle for supremacy, then making her choice. Threesomes or more-somes are not unknown. Frequent copulation is common, some pairs having sex around 50 times in just a few hours. These are highly productive couplings too, with females rarely missing an opportunity to fall pregnant.

So the answer to the question “Why don’t pandas have more sex?” is pretty simple. Because natural selection has resulted in a different way of doing it. Of course, none of this is going to stop the silly jokes about panda sex. So in the interest of balance, I like to imagine a pair of pandas sitting together in the forests of Sichuan, cracking bamboo in a moment of postcoital bliss and cracking jokes at the expense of humans, mocking their weird, drunken mating rituals, their single-bout sex and their frequent failure to conceive.

Five nights in Stanford

I’ve just returned from a mind-blowing trip to Stanford University, five days of back-to-back interviews with some of the most important figures in sleep research. It’ll all be in the book. This was made possible by a generous grant from The Society of Authors.

I got to meet William Dement, a legend in the field of sleep medicine and the reason why Stanford has such a high concentration of great doctors and researchers interested in sleep. I spent several delightful hours in the company of Christian Guilleminault, less well known than Dement but, in my view, an equal partner in the Stanford adventure.

Emmanuel Mignot (aka Dr Narcolepsy) gave me almost three hours of his time on President’s Day to talk through his work on the genetics and immunology of narcolepsy and more recent research on the genetics of Kleine-Levin Syndrome. He brought with him his dog Watson, a cute narcoleptic Chihuahua.

I met Samantha Lundquist, an animal behaviourist at the Penninsula Humane Society and owner of three huge dogs (one of them, Charlie, a narcoleptic). Neither dog experienced cataplexy in my company, which I was a little sad about, but I know better than anyone that cataplexy tends to come in the company of friends and not strangers.

I found out about some clever research that Jamie Zeitzer is involved with, using flashing lights to cause rapid shifts in the central circadian clock, which could be of immense benefit for shift-workers and would solve the problem of jetlag overnight. Quite literally.

I had an incredibly exciting time with Luis de Lecea, who was one of the researchers who first described hypocretins almost 20 years ago. He is using optogenetics and mice to understand the hypocretin pathway (and other neural networks). As a consequence he probably knows more about the myriad functions of this powerful neuromodulator than anyone alive. I was anxious that I would come out of this interview more confused than I went in (because the brain is so fiendishly complex) but I now have a very clear idea of the main functions that hypocretin performs, an insight that helps explain much about the narcoleptic condition (caused, of course, by a failure of the hypocretin system).

Using similarly cutting edge methods, Philippe Mourrain made a compelling case for using a simple animal model like the zebrafish to unpick the circuitry underlying sleep (rather than a crazily complex species like Homo sapiens). By tagging neurons with green fluorescent protein and because zebrafish larvae are transparent, it’s possible to see neurons firing in real time in a live animal in parts of the brain that in humans are buried far beneath the thick cortical surface. Yes, although fishes don’t close their eyes (they have no eyelids), they do sleep. They also have what looks like a rapid eye movement phase, except that Mourrain doesn’t like to call it REM because there’s no movement of the eyes. He prefers paradoxical sleep.

I also attended a lecture, part of the famous Sleep and Dreams course that Dement began at Stanford more than 40 years ago. Meir Kryger, who I’ve already interviewed about sleep apnea, was over from Yale University and spoke about the dangers of sleep deprivation and it’s implications for individuals and society.

All I have to do now is to get hours of interviews transcribed and written up while it’s still fresh. Gulp!

Lonesome George is back in Galapagos

Lonesome George,  (c) Henry Nicholls

Lonesome George the giant tortoise, the last individual of his species, has returned to Galapagos after an absence of almost five years. Following his unexpected death in 2012, the Galapagos National Park agreed to send him to a top-end taxidermist in New York. After painstaking treatment, George went on show at the American Museum of Natural History in 2014. He is now back in Galapagos, the centerpiece of a new exhibition aimed at visitors to the Fausto Llerena Breeding Center on Santa Cruz.

By the time I met Lonesome George during my first visit to Galapagos in 2003, he had become the face of extinction. I read the information panel around his enclosure: “Whatever happens to this animal, let him always remind us that the fate of all living things is in human hands.” I was not, however, overly impressed with this shy, retiring reptile and had no idea it was to be the beginning of a beautiful friendship.

Back at home in the UK, George’s influence on me started to grow. At the start of a career as a science journalist, I wrote about him, first a feature in Nature, then a popular science book called Lonesome George, until hardly a month would pass without me being called to comment on some aspect of his life. I should have become accustomed to George’s capacity to generate news, but every time he impressed me. There is no individual – animal or human – that could communicate the conservation message quite like George.

I love it that he’s still up to his old tricks, even in death. See also my Guardian blog Animal Magic.