Although the structure and organisation of the brain seems highly complicated, all the different parts boil down to the same fundamental building block: the neuron. The neuron is a special type of cell which processes and transmits information by electrochemical means. Neurons are found in the brain, the spinal chord, and in the nerves of the peripheral nervous system. They come in a great variety of shapes and sizes, however, most of them look like the one in the illustration below. Neurons are tiny. The cell body (soma) has a diameter of only 10-25 micrometres, which is just a little bit more than its cell nucleus. Their quantity, however, is immense. The human brain has roughly 100 billion neurons, each of them having several thousand connections to other neurons. This comes up to a whopping total of 500-1000 trillion connections within the brain. No computer on earth has that many connections or such a massively parallel organisation. At any rate, the often cited brain-computer analogy is inept. Nervous systems are a far cry from the simple feed forward input/output circuits of a contemporary computer. Unlike a computer, the brain is a living thing; it can grow and change; and the processes of neural conduction is much more complex than signal conduction in the logical gates of a computer chip.
Neurons, or nerve cells, are eukaryotic cells which resemble all other cells in the human body with one exception. They are specialised in conducting information. The neuron has several fundamental characteristics. It has an excitable membrane which allows it to generate or propagate electrical signals, a tree of dendrites which receive signals, and an axon that transmits signals. The axon is a cable-like fibre that transmits nerve impulses from the neuron to other neurons. Axons are only about one micrometre across, but they can become extremely long. For instance, the axons of the sciatic nerve in the human body may run a metre or longer from the spine to the toes. This could be compared to a 50 cm calibre pipeline that runs 2000 km long. A layer of fatty cells, the myelin sheath punctuated by the unsheathed nodes of Ranvier, insulates the axons of some neurons and speeds the impulses. Each neuron has only one axon which usually branches out extensively and passes signals to multiple target cells. Terminal buttons at the end of each axon branch connect the neuron to the receiver cells via synapses. Thus the synapse provides the functional connection between different cells. It consists of the target area, which may be a spine, a dendrite, or a cell body, and the synaptic gap between the axon terminal and the receiver cell. The dendrites are a branching arbour of cell projections that receive signals from terminal buttons which they conduct to the cell body.
Neural conduction
The principle of neural conduction can be described by neural impulses and synaptic transmission. These are two complementary methods of conduction which neurons are capable of. The neural impulse is either on or off, whereas synaptic conduction –based on the transmission of chemicals– is gradual. This can be likened to digital and analogue signal conduction. A neuron fires an impulse when it is stimulated by chemical messages from connected neurons, or by pressure, heat, or light. This impulse, called action potential, is caused by the depolarisation of the membrane potential of an excitable cell. Normally an electrical potential exists between the inside and outside of the cell. When ion channels in the cell membrane open, the exchange of ionised elements through the open channels causes an electric discharge. This impulse travels through the cell membrane and the axon hillock down to the axon and is then carried away from the cell. It propagates through the body at a speed of 10-100 metre per second, depending on the type of axon. The impulse doesn’t travel like an electrical signal, but rather through successive depolarisation of adjacent areas of the axon membrane, much like falling dominoes. During a very brief resting pause, the neuron pumps positively charged atoms back outside the membrane, after which the neuron is ready to fire again. This electrochemical process can be repeated 100 times per second.
Synaptic transmission is different. There are two type of synapses, electrical and chemical synapses. Electrical synapses couple neurons electrically via gap junctions. Chemical synapses work through the exchange of special chemicals called neurotransmitters. There are some 75 known neurotransmitters which amplify, relay, or modulate signals between neurons and other cells. These substances are produced by the soma, the chemical factory inside the neuron. The neurotransmitter molecules are usually packaged in spherical vesicles. These vesicles are conveyed through the axon towards the terminal buttons through special channels called microtubules, which are tiny pipelines running inside the axon. When a neural impulse reaches the knob-like terminals of the axon it triggers a biochemical cascade which causes the vesicles to fuse with the presynaptic membrane and release their neurotransmitters. The neurotransmitter molecules then cross the synaptic gap from the presynaptic membrane to the postsynaptic membrane within 1/10,000th of a second. It is like a very brief rain shower of neurotransmitters. Receptors on the postsynaptic membrane bind the neurotransmitter molecules. For a very brief period, ion channels on the postsynaptic membrane open to allow ions to rush in or out. This causes the transmembrane potential of the receiver cell to change. There are two types of changes. Depolarisation causes an excitatory postsynaptic potential; hyperpolarisation causes an inhibitory potential.
With this knowledge we can understand how neurons work together in the brain. Neuron A fires and reaches neuron B via the synapse AB. If the postsynaptic potential is excitatory and if it is strong enough to reach the action potential threshold, then neuron B fires. Synaptic strength is defined by the change in the transmembrane potential. If the potential does not reach the threshold value, neuron B might still fire if it simultaneously receives excitatory messages from other synapses. Thus multiple weak excitation can also trigger a postsynaptic action potential. On the other hand, neuron B might receive inhibitory messages from other synapses. In this case, neuron B might not fire, even if it receives a excitatory potential from a strong synapse. Thus a single neuron behaves a bit like a relay. This relatively simple behaviour lies at the root of neural firing patterns. The neuron’s status is either on or off, i.e. firing, or at rest. The complexity of neural firing patterns arises from the nature of synaptic connections. There is one thing we forgot to mention, however. What happens to the neurotransmitters after they are left in the synaptic gap? Obviously, multiple neurotransmitter releases from the terminal buttons would eventually accumulate and clog the synapse. However, this does not happen. There are two mechanisms that terminate synaptic transmission: reuptake and enzymatic degradation. The majority of neurotransmitters are almost immediately drawn back into the presynaptic buttons after release. There they are repackaged into vesicles and then recycled. This mechanism is known as reuptake. Other neurotransmitters are broken apart by enzymes after transmission and are thus deactivated.
Neurotransmitters and brain chemistry
Neurotransmitters are messenger substances. They can be classified into five different types of substances: amino acids, monoamines, neuropeptides, acetylcholine, and soluble gases. Amino acids are the most common neurotransmitters. Among them are glutamic acid and gamma-aminobutyric acid (GABA), which are the principal neurotransmitters in the human brain. Other well-known substances include noradrenalin, dopamine, and serotonin, which belong to the group of monoamines. Glutamate is the most prevalent excitatory neurotransmitter in the mammalian central nervous system, and GABA is the most prevalent inhibitory neurotransmitter. A neurotransmitter produces either excitation or inhibition. Only in rare cases, where the effect is dependent upon the receptor subtype, a neurotransmitter causes both inhibition and excitation. The receptor is the protein molecule in the postsynaptic cell that binds the neurotransmitter and initiates a reaction. Once again, there are different types of receptors, such as ion-channel linked receptors, chemically activated ion channels, and G-protein linked receptors. To simplify things, we can imagine neurotransmitters as keys to certain receptor locks, which –once unlocked– initiate an excitatory/inhibitory process in the postsynaptic cell.
Acetylcholine
Acetylcholine (ACh) is the messenger at junctions between motor neurons and muscle cells. When ACh is released to muscle cells, the muscle contracts. If ACh release is blocked, the muscle cannot contract. Curare, the poison used by South American Indians for hunting with darts, blocks ACh receptors and thus paralyses the victim. Curare leads to death through suffocation, because the victim cannot contract the respiratory muscles anymore. By contrast, the neurotoxin of the black widow spider triggers a synaptic flooding of ACh, and thus causes painful contractions, convulsions, and possible death.
Glutamic acid and GABA
Glutamic acid (glutamate) and Gamma-aminobutyric acid (GABA) are the excitatory and inhibitory workhorse neurotransmitters of the nervous system. It is believed that glutamic acid is involved in cognitive functions, such as memorising and learning, because of its role in synaptic plasticity. Glutamic acid overstimulation is associated with diseases like amyotrophic lateral sclerosis, lathyrism, and Alzheimer's disease. Glutamic acid excess can cause neuronal damage and eventual cell death. Glutamic acid is also the precursor of GABA which is synthesised with the help of an enzyme whereby the excitatory neurotransmitter is converted into an inhibitory one.
Dopamine
Dopamine is crucial to physical and mental health. It has a role in movement, cognition, pleasure, and motivation. Neurons containing the neurotransmitter dopamine are clustered in the midbrain in an area called the substantia nigra. A shortage of dopamine and the death of dopamine neurons causes Parkinson’s disease which is associated with depression and the loss of control of movement. Dopamine in the frontal lobe regulates the information flow from other areas of the brain which is vital to memory, attention, and problem solving. Dopamin depletion in the prefrontal cortex is associated with attention deficit disorder and schizophrenia. Disruptions of the dopamine system are also linked with psychosis. However, the most recognised role of dopamine in the brain is providing pleasure and enjoyment, hence, dopamine has also been termed the "reward chemical". Dopamine is released in the course of rewarding experiences such as food, sex, and other stimulating experiences.
Epinephrine and norepinephrine
Epinephrine (adrenaline) and norepinephrine (noradrenaline) are the body’s stress hormones which are typically involved in fight-or-flight situations. Epinephrine and norepinephrine are released into the bloodstream from the ardrenal medulla. The secretion of these substances is the physiological response to a threatening or exciting situation. Environmental stressors (such as bright lights, piercing noise, etc.) also cause release. The two substances are structurally very similar and they function both as neurotransmitters and hormones. As neurotransmitters they mediate chemical communication in the sympathetic nervous system, a branch of the autonomic nervous system. Among the major effects mediated by epinephrine and norepinephrine are increased heart rate, blood vessel constriction and increased arterial blood pressure, dilation of bronchioles assisting in pulmonary ventilation, stimulation of the fat burning process, dilation of pupils, increase of metabolic rate and muscle readiness, and inhibition of non-essential function, such as digestion.
Serotonin
Serotonin is an important neurotransmitter synthesised by so-called serotonergic neurons in the brainstem. The serotonin system is the largest single system in the brain, influencing a broad range of basic functions. Serotonin is important, because it plays a key role in the regulation of mood, sleep, appetite, vomiting, and sexuality, and because it is associated with a host of mental disorders, such as depression, bipolar disorder, and anxiety. Serotonin differs from other neurotransmitters in one respect. It is able to modulate the effect of other neurotransmitters, making it effectively a "master" neurotransmitter. Serotonin is known to unlock 14 or more different receptor subtypes, each of which has a distinct function in regulating impulses, motivation, moods, and appetite. Low moods and low motivation are associated with low serotonin levels. There are antidepressants on the market, e.g. Prozac, Zoloft, and Paxil, which act as serotonin reuptake inhibitors and thus increase the availability of serotonin in the brain. Other medications increase the serotonin reuptake and reduce serotonin levels. These medications are used to aid or tweak an imbalanced serotonin system.
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