The Spark of Life: Electricity in the Human Body

by Ashcroft, Frances

  Referring to the story, Quintilian recommends that when learning a long text you should break it up into shorter pieces. Then you should visualize a familiar place – your home, for example – and put different bits of the text in different rooms. To recall the text again, you just walk through the imaginary house, room by room, recollecting the text as you go. The place method, and continual repetition, are still the best ways to remember something and are often used by memory savants today.

  Remembrance of Things Past

  Exactly how and where memories are stored in the brain is still unclear. The fact that stimulation of certain bits of the brain can evoke vivid memories of things past – a familiar scent, a snatch of a song, even the complete recall of an event with all its sensations intact – suggests that at least some memories are stored in certain specific brain locations. People who suffer from visual agnosia may lose the ability to recognize particular objects, despite their senses and memory being intact. As Oliver Sacks relates in his book The Man Who Mistook His Wife for a Hat, they can describe what a glove looks like, but may be quite unable to recognize that it is, in fact, a glove, or know what it is used for. They may also fail to recognize one person, but not another, or confuse their wife with their hat. All this suggests that there may be discrete regions of the brain that are used for processing and storing specific types of information.

  There is also a distinction between short-term and long-term memory. You use the former when you remember a number for a few minutes, or plan the outcome of a series of chess moves before you decide which one to use. Short-term (or working) memory seems to involve regions within the cortex, particularly the frontal lobes. Long-term memory enables us to recall events from our childhood. The fact that most people fail to recollect many events before the age of about three suggests that long-term memory storage may not be fully developed until then. How working memories are selected for long-term storage, how, where and in what form they are laid down, and how they are retrieved is currently under intensive investigation.

  One brain region of key importance for memory storage is the hippocampus, so called because it is shaped like a seahorse. We have two of them, one on each side of the brain. Their role was discovered serendipitously by studies of Henry Gustav Molaison, better known to scientists as HM. As a young boy, HM suffered from intractable epilepsy. In an attempt to cure his seizures, most of the hippocampus on both sides of his brain was removed when he was twenty-seven. The consequence was disastrous for HM (but a goldmine for science), as he lost the ability to make new memories and his memory of some preceding events was also impaired. He was confined to living in the past. Nevertheless, he was able to perform tasks that need only short-term memory, clearly demonstrating that short-term and long-term memory are distinct. His ability to learn new motor skills was also intact; he became an accomplished table-tennis player, despite being adamant he had never played it before. He was also a gracious, patient and modest individual whom the researchers he worked with considered as one of the family, although he never recognized who they were, even if they returned just a few minutes after leaving the room.

  The hippocampus is particularly important for spatial memory – for our ability to recall places. Taxi drivers who have to memorize the streets of London, information colloquially known as the ‘Knowledge’, tend to have larger hippocampi than the rest of us. Brain imaging has revealed that their hippocampi also light up when they are planning a route; simply thinking about how they might travel from Paddington Station to Buckingham Palace activates this bit of the brain. Fascinatingly, when they cease to use the ‘Knowledge’ regularly their hippocampi revert back to the same size as ours. ‘Lose it or use it’ seems to be an aphorism that is as valid for the brain as for your muscles.

  It turns out that we construct a spatial map of our environment inside our heads, which can even be detected at the level of single hippocampal neurones. Nerve cells known as ‘place cells’ increase their activity only when an animal is in a specific location in its environment. As a rat runs along a corridor, for example, an individual cell bursts into activity and then ceases to fire as the animal enters and leaves the location corresponding to its ‘place field.’ Multiple neurones, each with a different place field, together provide an ‘electrical map’ of the whole environment. This map is established within minutes of entering a new environment, and if the animal is returned to the same environment a few days later, the same nerve cells fire at exactly the same location. Thus this spatial reference map may be involved in formation of spatial memories.

  Although the hippocampus is crucially involved in laying down long-term memories, most memories are not actually stored there. Many other bits of the brain appear to be involved. Imagine you are watching an opera – The Magic Flute, for example. Your eyes capture the image of the Queen of the Night robed in a gorgeously coloured gown, and your ears pick up the wonderful aria she sings. These are relayed to the visual and auditory cortex respectively, where they are interpreted, and linked together to create a picture of the scene. The information is then forwarded to the hippocampus, which decides whether to pass it on to your long-term memory. If it does, the information is relayed back to the appropriate cortical areas, where it is laid down as new synapses or existing connections are strengthened. Information is thus circulated around the brain; it is not a matter of it being channelled straight from the eyes to your memory, but of a complex series of information-processing events that take place in multiple different brain regions.

  The hippocampus enables associations between sensations and experiences to be hard-wired, enabling you to ‘play back’ a scene from memory. Damage to this bit of the brain affects your ability to store new memories. However, memory formation does not only involve the hippocampus. The amygdala also plays a part in memory consolidation. How interested you are in an event and what emotional associations it has for you will influence your ability to recall it later. This is why most of us will remember events such as the birth of our child or where we were when we heard that the Twin Towers of the World Trade Center had collapsed, but will probably quickly forget what we were doing at lunchtime last Tuesday.

  Memories of mechanical skills are stored separately and are not channelled through the hippocampus. Your ability to remember how to ride a bike even though you have not done so for many years is stored in your cerebellum and motor cortex. This is why it is still possible for people to play music despite having lost much of their memory of places and events, and why HM was able to play table tennis.

  Memories are Made of This

  How memories are laid down appears to involve changes in the physical structure of the brain. Contrary to what was once believed, your brain is not a static structure, but extraordinarily adaptable. New connections between nerve cells are continuously being made and existing ones strengthened or eliminated as you go about your daily life. This process, known as synaptic plasticity, is the physical basis of learning and memory.

  The fine filaments – the dendrites – that extend outwards from the nerve cells in your brain are covered in tiny knob-like extensions called spines. Thousands of them decorate a single dendrite. The dendritic spines are the sites of the synapses and it is here that memories are hard-wired, for as we learn new things and lay down new memories, new spines appear and existing ones change shape or disappear. As they grow in size and number so a particular neuronal pathway is reinforced. Such reinforcement often happens when connections between neurones are simultaneously activated, and has given rise to the neuroscientists’ adage ‘Cells that fire together, wire together.’ This happens very rapidly. Experiments in mice have shown that learning to press a button to obtain a food reward is associated with a dramatic increase in new synapses within just an hour of starting training. Strikingly, in these experiments, the new spines endured long after training had ceased, but the total number gradually returned to the pre-training level because older ones were eliminated. Perhaps the brain can only
support a finite number of connections, which is why learning new things may reduce our capacity to remember older events. Ion channels lie at the heart of memory for the presence of different kinds of glutamate receptor channels is necessary both to retain existing synapses and to grow new ones. If these channels are absent, or their function is impaired, our ability to remember is reduced.

  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 bypas
s 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.