The brain in a nutshell

This essay I wrote was shortlisted in the Association of British Science Writers competition in 2002. It was the first thing I posted on the old blog.

It was written as an introduction to what were generally believed to be the fundamentals of brain function, starting from the molecular level and working all the way up.

But our understanding of the brain has advanced dramatically since then, and there is now evidence to suggest that some of these assumptions are now wrong. 

For example, it was, I think, taken for granted that all neurons fire action potentials, but it now appears that some neurons at least are capable of propagating signals without them.

Nevertheless, it's probably still worth reading.

The seat of all human behaviour, of emotions, memory and consciousness, the human brain is the most complex structure known to science, containing hundreds of billions of connected, communicating cells. Scientists know more about the universe than about the brain, which really is the final frontier of human knowledge.

Although the roots of neurology and neuroscience can be traced back as far as Ancient Egypt, it is only in the last 150 years that we have gained any real understanding of the brain. Advances in DNA technology have, in the last few decades, allowed researchers to investigate the brain in detail previously unimaginable.

Nervous systems evolved to detect and respond to novel stimuli in the environment, stimuli which may be relevant to the survival of the organism. The crucial word in the last sentence is "novel," for if a stimulus remains unchanging for some time the brain ignores it. This can easily be tested by holding someone's hand and remaining motionless for some time. Shortly you will realize that you cannot feel the hand you are holding until, that is, either of you makes the smallest of hand movements. This changes the tactile stimuli received by the hand, and the brain makes you aware of it.

Although there are many thousands of types of neuron, they all have the same basic structure. At one end the dendrites, or branches, receive inputs from other cells and send them to the cell body, where integration of all the inputs takes place. The output of the neuron, in the form of a specific pattern of electrical activity, is sent along the axon, and then transmitted to up to 1 million other neurons.

Neurons are specialized to generate and transmit electrical signals to one another. The membranes of all types of cell are said to be polarized - that is, there is an unequal distribution of electrical charge (in the form of ions, or charged atoms) on either side of the membrane, with positive ions concentrated on the outside of the membrane and negative ions on the inside.

When a neuron is inactive, the average resting 'potential,' or charge, of the inside of a neuron, with respect to outside the cell, is -70 millivolts (mV, thousandths of a volt). Neurons differ from other cells in that they are capable of transiently reversing the distribution of charge around the membrane, and this, in essence, is the nervous impulse, or 'action potential.' Within thousandths of a second, the charge on the inside of the nerve cell membrane is reversed (or 'depolarized') to +120 mV, before reverting to its original state ('repolarized'). When returning to its original state, the cell actually becomes too negatively charged than it first was. In this state, called hyperpolarization, the voltage of the cell membrane reaches -120 mV for a brief period, rendering the cell incapable of generating another action potential. The timescale on which this occurs means that an individual neuron can generate hundreds of action potentials every second.

How is the voltage of the neuron's membrane reversed? It has to do with the properties of the neuron's cell membrane. The membrane acts as a capacitor - in other words it can store electrical charge. It is also an insulator, preventing electrical charge from leaking in or out of the cell but at the same time allowing positive or negative currents to flow across the membrane when needed. Barrel-shaped protein molecules called voltage-gated ion channels, embedded in the neuron's cell membrane, regulate the flow of ions in and out of the cell. The three-dimensional structure of each of these molecules changes in response to changes in the voltage across the cell's membrane, selectively allowing a certain species of ion to flow across the membrane in one or the other direction. The exact structure inside the barrel-shaped channel determines which type of ion can pass through it when opened. A channel selective for positive ions will have negatively charged amino acid residues lining the inside of the barrel-shaped part of its structure, and vice versa for a channel selective for positive ions. The diameter of the channel will correspond to the size the ion it is selective for.

Voltage-gated sodium channels, when open, allow positively charged sodium ions to enter the cell. This occurs because there is a so-called concentration gradient of sodium ions around the membrane, as a result of the unequal distribution of the ions. Sodium ions are more highly concentrated outside the cell than in, so they would tend to want to enter the cell, but are prevented from doing so when the cell is resting. That is, they would normally move down the concentration gradient from an area of high concentration to one of low concentration. The opposite situation is true for negatively charged chloride ions. So, it is the influx of sodium ions, through these sodium ion channels that causes the reversal of membrane voltage, and the flow of chloride ions through chloride channels which reverts it to its resting state.

By repetition of this process, the reversal of the membrane voltage, along the length of the cell, cause the nervous impulse to be propagated from one end to the other. But the electrical signal cannot jump the miniscule gap at the junction (or 'synapse') between two neurons. The electrical signal therefore is converted to a chemical one, which is transmitted across the synapse, to the next neuron. Small molecules called neurotransmitters (such as dopamine, serotonin and acetylcholine) are stored in vesicles which are clustered around the neuron's terminal. In response to an impulse reaching the nerve terminal, the vesicles fuse with nerve terminal membrane and release their contents into the space between the two connected cells. The neurotransmitter molecules diffuse across the space, which is mere 40 nanometers (nm, millionths a millimeter) wide, and bind to receptor proteins embedded in the adjacent cell. This binding initiates a nervous impulse in that cell. Once its job is complete, the neurotransmitter molecules are taken up by the cell that released them and a re recycled back into vesicles for re-use.

Neurotransmitters can also act at sites other than synapses to modulate the activities of cells. As if things weren't already complicated enough, molecules that play roles in processes unrelated to nervous system function are sometimes found to be used as neurotransmitters by neurons, an example being nitric oxide (NO), a gas only recently discovered as having a role in neurotransmission.

This process, neurotransmission, can occur between two cells many times each second. Certain types of neurons will transmit to more than one other cell simultaneously. Many drugs interfere with neurotransmission in one way or another, perhaps by mimicking the actions of a neurotransmitter. This is the case for cocaine and methamphetamine (Ecstasy), which mimic the actions of noradrenaline. Anti-depressants like Prozac, for example, prevent the uptake of serotonin into the cell after neurotransmission, hence their name, specific serotonin-reuptake inhibitors (SSRIs).

The action potentials produced in different neurons are basically the same, with small differences in size and timing. The action potential itself does not contain information. It is the connectivity of the brain that is crucial here - the information carried by an action potential, or a series of them, depends on the location of the cells sending the impulses. Information is also contained within the frequency of the impulses. What is the nature of this information which neurons send to one another? We can think of a neuron as a binary electrical switch, in the sense that its job is to generate a pulse of electricity (the action potential), and that at any given moment it is either generating one or it isn't, that is, it is either on or off. Information received by a neuron makes it more or less likely to generate an action potential, or affects the frequency of action potentials it is generating.     (Update)

We can consider brain function as the integration of thousands of specialized modules, each one consisting of many millions of a unique type of neuron, adapted to a particular function. The cells making up each module can act in synchrony, with their collective electrical signals communicating with other modules involved in the same function. There is a region specialized for processing visual information (the visual cortex), one for hearing, one for smell, and several for speech. There are regions specialized for the recognition of faces and facial expressions. Each of these modules can be seen as independently functioning, but most behaviours, such as walking or talking, require the integrated actions of many modules. 

Most of these independently functioning modules are contained within the neocortex of the human brain. The cortex (meaning bark in Latin) is the most prominent feature of the human brain and its enlargement is what distinguishes us from other animals. The human neocortex, which is approximately one centimeter thick, is actually several meters squared in size when unraveled. Yet it is convoluted to such a degree that it is contained within the skull. Apart from the obvious advantage of saving space, the convolution of the cortex brings all the functioning modules within close proximity of each other so that they may effectively communicate with each other. Primitive functions such as breathing are controlled by the inner regions of the brain, the subcortical ('under the cortex') structures, which are really an extension of the spinal cord. These regions are collectively called the brain stem; from an evolutionary perspective, we can call the brain stem the amphibian brain.

At a higher level of organization, groups of these modules are interconnected to form systems within the brain. We can speak of the visual system, for example, as meaning all the brain regions involved in vision. This would include the retina, at the back of the eye, whose photoreceptor cells convert light energy into nervous impulses (i.e. they are transducers). These cells transmit the information to regions of a sub cortical structure called the thalamus, via the optic nerve. The final processing of visual information takes place in the visual cortex, which receives inputs from the visual regions of the thalamus. Here, the information is refined by passing successively through primary secondary and tertiary cortical regions. Within the visual cortex are many different kinds of neurons each specialized to transmit information regarding a certain aspect of the visual world, such as colour, shape or contrast.

Neurology is largely based on the clinical observations of brain-damaged people. In the nineteenth century, on examining the brains of deceased stroke victims, Paul Broca found that they all had in common damage to a particular region of the left hemisphere of the brain. A common symptom of stroke is aphasia, or an inability speak, which occurs as a result of damage to Broca's area, due to a lack of oxygen. Close to Broca's area is an region discovered by Wernicke, involved in the comprehension of speech.

A century after Broca, the neurosurgeon Wilder Penfield made huge advances in our understanding of the organization of the motor cortex. By electrically stimulating the motor cortex during surgical procedures, he elicited involuntary movements in his patients. Successive stimulation of adjacent areas of motor cortex resulted in the movement of adjacent parts of the body. Every square millimeter of skin of the human body sends nervous connections to the somatosensory cortex. Similarly, every muscle in the body is connected indirectly to the motor cortex. The area of space in the brain devoted to a particular part of the body is proportional to the number of muscles in that part. Hence the face, with over 100 muscles, has a large part of the somatosensory and motor cortices controlling it, as do the hands. Broca's area is in fact part of the motor cortex, and is involved in controlling the muscles in the tongue and throat required for speech.