The Spark of Life: Electricity in the Human Body (35 page)

As we grow older our remembrance of things past often seems to diminish. The semi-photographic memory I had as a child has long since vanished and my ability to recall names and faces is now embarrassingly poor. But this is nothing compared with the trauma of Alzheimer’s disease, which afflicts around half a million people in the UK. It is the most frightening of diseases for it steals away the soul. At first it may seem as if the victim has no more than mild memory loss, but with time they lose all recollection of friends and family, become confused, withdrawn and increasingly distressed.

Alzheimer’s disease is characterized by the loss of neurones and synaptic connections in the cerebral cortex, resulting in a reduction in the size of the brain. Tangled networks of a protein known as tau appear inside nerve cells and dense plaques of amyloid protein are found in the space between nerve cells. Whether these are the cause or the consequence of cell death is unknown. The electrical activity of the brain is clearly impaired, but again whether this is merely due to the loss of nerve cells, is produced by the observed reduction in dendritic spines, or results from impaired transmission between nerve cells is unclear. One idea is that the disease leads to a reduction in the amount of acetylcholine in certain regions of the brain, and thus drugs that block the breakdown of the transmitter are currently used as therapy to boost its levels. They are not very effective, however, merely slowing the progression of the disease. Nothing has been found that can stop it in its tracks or reverse its effects. At present, Alzheimer’s disease has no cure and remains a tragedy for both the patient and their family.

Shedding Light on Behaviour

Understanding exactly how the brain controls a particular behaviour is far from easy. One approach has been to try to tease apart the precise contributions of individual neurones. Recent pioneering work by Oxford University professor Gero Miesenböck has led to a revolutionary new field of neuroscience called optogenetics which enables a particular group of nerve cells to be turned on (or off) at will, without affecting the activity of adjacent neurones. In this way, it is possible to control the behaviour of an animal simply by switching on a light. The technique utilizes ion channels that act as light-activated molecular switches. These are inserted into a specific set of nerve cells by genetic manipulation, where they sit quietly shut, without any effect on the cells’ electrical activity, until the researcher chooses to open them by illuminating them with an intense pulse of laser light of a particular wavelength. One of these light-activated ion channels, known as channel rhodopsin, comes from a green alga. Simply switching on the laser light opens the channel, leading to an influx of positively charged ions that stimulates the cell into activity. Because the duration and timing of the laser pulse can be precisely controlled it is possible to mimic the activity of individual nerve cells and thus investigate how different patterns of activity influence behaviour. In a similar fashion it is possible to turn off the electrical activity of a nerve cell using a different kind of light-activated ion channel that clamps the cell at the resting membrane potential when it is opened.

To woo a mate, the male fruit fly sings to her by rapidly vibrating his wings. Miesenböck was fascinated by the fact that although the brains of male and female flies seem to be wired up in much the same way, their behaviour is very different. His team found that by switching on a specific group of neurones with a light pulse, female flies could be coaxed into producing the male courtship song. It is as if the fruit fly has a ‘unisex’ brain that is directed to produce different patterns of behaviour – male or female – by a few neuronal master switches. If the correct nerve cells are stimulated, a fly can even ‘learn’ from an experience it has never had. While it is relatively easy to control a fruit fly’s behaviour with light, it is more difficult to do so in a mammal, as the laser beam cannot penetrate the skull and light must be delivered by a fibre-optic cable implanted in the brain. Nevertheless, it has also proved possible to control the behaviour of a mouse this way. Optogenetics promises to be a valuable tool for illuminating how the brain controls behaviour.

Just as the fruit fly’s courtship song-and-dance routine is hard-wired, so too are other forms of social behaviour. Moreover, experience physically shapes our brains, which helps explain why identical twins, despite having exactly the same genetic constitution, are quite different people. This is beautifully illustrated by the social hierarchy of the crayfish. When challenged, a crayfish will back out of a potentially threatening situation using a tail flick that catapults it rapidly backwards. If two crayfish are placed in the same tank, one quickly becomes dominant and the other subordinate, and this is paralleled by a marked difference in the electrical responses of the giant nerve fibres that control the tail flip, and in the effect that the neurotransmitter serotonin has on these cells. If the dominant animal is removed from the tank, the subordinate one then adopts a dominant electrical response by changing the way in which serotonin acts on its nerve cells. Fascinatingly, once a crayfish has experienced being the alpha animal for a while it never looks back. Although it may revert to subordinate behaviour if a more aggressive crayfish is reintroduced into the tank and it loses a fight, the ‘dominant’ effect of serotonin remains unchanged. In a kind of neurological denial it has forever a dominant brain. Reality television programmes in which individuals play different roles in Edwardian society reveal that people quickly assume servant or master roles. An interesting question is the extent to which such role-playing may have physically changed their brains.

To Sleep, Perchance to Dream

Sleep is so familiar that we rarely think about it. Every night when we fall asleep we surrender our consciousness, our muscles relax and our ability to respond to mild stimuli is diminished. Sleep is associated with characteristic changes in the electrical activity of our brain, but this is not simply a global suppression of nerve cell function but a highly controlled phenomenon. Although we commonly think of sleep as a single state it actually comprises two quite distinct brain states, known as rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. Throughout the night, periods of REM sleep alternate with those of NREM sleep. Each of these sleep cycles lasts about ninety minutes and you will have about four or five of them a night. In total, around 25 per cent of the time you spend sleeping, amounting to between one and a half to two hours a night, is spent in REM sleep, with its duration increasing in each sleep cycle as night moves towards morning.

As you fall asleep, you first enter a transient dream-like state between sleeping and waking. This twilight zone lasts just a few minutes, after which you enter a period of NREM sleep. As you do so, your EEG pattern changes, passing through various stages of light sleep before finally settling down to the slow, rolling, low-frequency brain waves of deep sleep. Your muscles relax and your ability to respond to external stimuli diminishes. Brain activity in many areas, particularly the cerebral cortex, is reduced and you are now hard to wake.

Astonishingly, after you have been sleeping for about an hour or so everything abruptly changes. Despite remaining sound asleep, your brain appears to wake up and your EEG becomes a frenzy of rapid low-voltage, high-frequency waves. Many areas of your brain become activated, with particularly intense activity occurring in regions associated with the emotions, such as the amygdala. This is a time of intense dreaming and if you are woken you are likely to remember your dreams. Your muscles are paralysed by inhibitory signals sent from the brainstem to the muscles to prevent you damaging yourself by acting out your dreams. The only muscles that remain active are your respiratory muscles (fortunately) and those of your eyes, which are connected directly to your brain and therefore bypass the inhibitory pathways in your brainstem. Flurries of rapid eye flickers occur, which is why this stage of sleep is known as rapid eye movement (REM) sleep. If the brainstem is damaged, the ability to inhibit muscle movements during sleep may be lost and such unfortunate people may get out of bed and move about during their dreams: they may even need physically restraining to prevent them from hurting themselves or their sleeping partners. When you exit REM sleep, muscular control is automatically re-engaged. In some rare individuals this does not happen immediately and they may wake to find themselves temporarily paralysed, a truly frightening experience.

During REM sleep your senses are also disconnected from your brain so that you are cut off from the world. The brain region known as the thalamus relays sensory information from our sense organs up to the cerebral cortex, but during sleep this pathway is largely closed, so little gets through. We are walled off from the world, in sensory isolation and unable to command the use of our muscles, but our brains are on overdrive. It is rather like a car whose engine is revving, but which cannot move because the gears are not engaged. Sleep, then, is a dynamic activity. Your brain does not simply switch off, but instead refocuses its activity differently.

At some time of our life, we have all felt unaccountably sleepy during the day – often as a consequence of jet-lag – but for some unfortunate people excessive sleepiness is more of a problem. Take Claire, for example, who abruptly and embarrassingly falls asleep at inopportune moments and is quite unable to do anything about it. She also once laughed so much at her friend’s joke that her legs gave way and she collapsed on the floor; indeed any form of excessive excitement or strong emotion can cause a loss of muscle tone so profound that she becomes floppy and falls over. Claire suffers from a chronic sleep disorder known as narcolepsy that is characterized by excessive daytime sleepiness despite adequate night-time sleep. The lack of muscle control she experiences is known as cataplexy and arises because the inhibitory pathways that prevent us moving during sleep are inappropriately switched on during wakefulness or very early in the sleep cycle.

A group of scientists led by Emmanuel Mignot investigated a strain of Doberman pinscher dogs that suffered from the same condition as Claire. Spotting a special food treat, one of these dogs will rush happily over and take a few mouthfuls, but after a few seconds will be so overcome by the excitement that it loses control of its limbs and collapses. The condition is inherited and by laboriously searching for the gene involved scientists identified a chemical called orexin (or hypocretin) that helps stop us falling asleep. This is produced by a small region of our hypothalamus and keeps us awake by stimulating electrical activity in other regions of the brain. If you lack the ability to make orexins, or you have insufficient orexin receptors (as the Doberman dogs did), you will fall asleep involuntarily.

Sleep is a universal imperative. All animals sleep, even insects and fish, and while we proverbially manage an average of eight hours a night, some creatures sleep for far longer. The champion is the two-toed sloth, which sleeps as much as twenty hours each day. Mammals that live in the sea would drown if they fell sleep underwater, so they rest half of their brain at a time, with one side remaining awake while the other is deeply asleep. So too do many birds, which often sleep away the night with one eye open, keeping watch for predators.

Quite why we sleep is still something of a mystery, but there is evidence that one reason is that it is important for memory consolidation. As you will no doubt already know from experience, without adequate sleep our ability to remember things diminishes. Strikingly, even a short nap can help with learning a new task. One hypothesis is that while we are laying down long-term memories, and consolidating and organizing new knowledge, it is important that there is no new input to confuse things. Cut off from the outside world, memories can be replayed, strengthened, stored or discarded more easily. Some evidence in favour of this view comes from the finding that during sleep hippocampal ‘place cells’ fire in a coordinated fashion that suggests the spatial reference map that is formed in the brain when an animal is exposed to a new environment is being replayed. It is as if the brain is remembering its earlier experience – although whether this replay is associated with the consolidation of memory or the transfer of memories out of the hippocampus to areas of the brain where memories are stored is still unknown.

Whatever its actual function, sleep is essential, for without it we soon die. Sleep, then, is very far from the ‘little slice of death’ that Edgar Allan Poe bewailed. Nor is it a nightly waste of time. Rather, as Shakespeare put it, it is ‘the chief nourisher in life’s feast
^’
and we should endeavour to make sure we get enough.

The God of Dreams

Once, when I was a child, my whole family came down with severe gastroenteritis. Both my parents and my siblings were hors de combat and I was the only person available to collect the medicine. We lived in an isolated village and there were no buses running at the time, so I jumped on my bicycle and pedalled the five miles to the doctor’s surgery. I was given a large glass bottle of kaolin and morphine that I stuffed in my jacket pocket. The journey back was something of a nightmare as it soon became clear that I too was suffering from the vomiting bug and I had to stop several times to throw up on the verge. I arrived home completely exhausted. My mother immediately gave me a large dose of medicine, but, being ill herself, she did not think to shake the bottle first. During the long journey, the kaolin had settled to the bottom and floating at the top was a (weak) solution of pure morphine. Morphine, named after Morpheus, the Greek god of sleep, is a powerful sedative and I slept for twenty-four hours.

Morphine is not only a sedative. It also produces relaxation, induces a state of delightful, dreamy euphoria and has the great virtue of relieving pain. It has been used for thousands of years, as both a medicinal and a recreational drug, in the form of opium, a crude extract of the opium poppy,
Papaver somniferum
. As the seventeenth-century physician Thomas Sydenham said, ‘among the remedies it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium’. Historically, a mixture of opium and alcohol called laudanum was used to treat a variety of ailments and as a consequence many people became addicted, including the poet Samuel Coleridge, who is believed to have written ‘Kubla Khan’ while under the influence of the drug. Others took it for pleasure. Thomas de Quincey wrote in his famous
Confessions of an English Opium Eater
, ‘I, wretch that I am, being so notoriously charmed by fairies against pain, must have resorted to opium in the abominable character of an adventurous voluptuary, angling in all streams for a variety of pleasures.’