The Human Nervous System
Humans, like all living organisms, can respond to their environment. Humans have two complimentary control systems to do this: the nervous system and the endocrine (hormonal) system. We’ll look at the endocrine system later, but first we’ll look at the nervous system. The human nervous system controls everything from breathing and producing digestive enzymes, to memory and intelligence.
The nervous system composed of nerve cells, or neurones:
A neurone has a cell body with extensions leading off it. Numerous dendrons and dendrites provide a large surface area for connecting with other neurones, and carry nerve impulses towards the cell body. A single long axon carries the nerve impulse away from the cell body. The axon is only 10µm in diameter but can be up to 4m in length in a large animal (a piece of spaghetti the same shape would be 400m long)! Most neurones have many companion cells called Schwann cells, which wrap their cell membrane around the axon many times in a spiral to form a thick insulating lipid layer called the myelin sheath. Nerve impulse can be passed from the axon of one neurone to the dendron of another at a synapse. A nerve is a discrete bundle of several thousand neurone axons.
Humans have three types of neurone:
The three types of neurones are arranged in circuits and networks, the simplest of which is the reflex arc.
In a simple reflex arc, such as the knee jerk, a stimulus is detected by a receptor cell, which synapses with a sensory neurone. The sensory neurone carries the impulse from site of the stimulus to the central nervous system (the brain or spinal cord), where it synapses with an interneurone. The interneurone synapses with a motor neurone, which carries the nerve impulse out to an effector, such as a muscle, which responds by contracting.
Reflex arc can also be represented by a simple flow diagram:
The Organisation Of The Human Nervous System
The human nervous system is far more complex than a simple reflex arc, although the same stages still apply. The organisation of the human nervous system is shown in this diagram:
It is easy to forget that much of the human nervous system is concerned with routine, involuntary jobs, such as homeostasis, digestion, posture, breathing, etc. This is the job of the autonomic nervous system, and its motor functions are split into two divisions, with anatomically distinct neurones. Most body organs are innervated by two separate sets of motor neurones; one from the sympathetic system and one from the parasympathetic system. These neurones have opposite (or antagonistic) effects. In general the sympathetic system stimulates the "fight or flight" responses to threatening situations, while the parasympathetic system relaxes the body. The details are listed in this table:
Inhibits saliva production
Speeds up heart rate
Stimulates glucose production
Stimulates tear secretion
Stimulates saliva production
Slows down heart rate
Stimulates bile production
Neurones and muscle cells are electrically excitable cells, which means that they can transmit electrical nerve impulses. These impulses are due to events in the cell membrane, so to understand the nerve impulse we need to revise some properties of cell membranes.
The Membrane Potential
All animal cell membranes contain a protein pump called the Na+K+ATPase. This uses the energy from ATP splitting to simultaneously pump 3 sodium ions out of the cell and 2 potassium ions in. If this was to continue unchecked there would be no sodium or potassium ions left to pump, but there are also sodium and potassium ion channels in the membrane. These channels are normally closed, but even when closed, they "leak", allowing sodium ions to leak in and potassium ions to leak out, down their respective concentration gradients.
The combination of the Na+K+ATPase pump and the leak channels cause a stable imbalance of Na+ and K+ ions across the membrane. This imbalance causes a potential difference across all animal cell membranes, called the membrane potential. The membrane potential is always negative inside the cell, and varies in size from –20 to –200 mV in different cells and species. The Na+K+ATPase is thought to have evolved as an osmoregulator to keep the internal water potential high and so stop water entering animal cells and bursting them. Plant cells don’t need this as they have strong cells walls to prevent bursting.
The Action Potential
In nerve and muscle cells the membranes are electrically excitable, which means that they can change their membrane potential, and this is the basis of the nerve impulse. The sodium and potassium channels in these cells are voltage-gated, which means that they can open and close depending on the voltage across the membrane.
The nature of the nerve impulse was discovered by Hodgkin, Huxley and Katz in Plymouth in the 1940s, for which work they received a Nobel prize in 1963. They used squid giant neurones, whose axons are almost 1mm in diameter, big enough to insert wire electrodes so that they could measure the potential difference across the cell membrane. In a typical experiment they would apply an electrical pulse at one end of an axon and measure the voltage changes at the other end, using an oscilloscope:
The normal membrane potential of these nerve cells is –70mV (inside the axon), and since this potential can change in nerve cells it is called the resting potential. When a stimulating pulse was applied a brief reversal of the membrane potential, lasting about a millisecond, was recorded. This brief reversal is called the action potential:
The action potential has 2 phases called depolarisation and repolarisation.
Depolarisation. The stimulating electrodes cause the membrane potential to change a little. The voltage-gated ion channels can detect this change, and when the potential reaches –30mV the sodium channels open for 0.5ms. The causes sodium ions to rush in, making the inside of the cell more positive. This phase is referred to as a depolarisation since the normal voltage polarity (negative inside) is reversed (becomes positive inside).
Repolarisation. When the membrane potential reaches 0V, the potassium channels open for 0.5ms, causing potassium ions to rush out, making the inside more negative again. Since this restores the original polarity, it is called repolarisation.
The Na+K+ATPase pump runs continuously, restoring the resting concentrations of sodium and potassium ions.
How do Nerve Impulses Start?
In the squid experiments the action potential was initiated by the stimulating electrodes. In living cells they are started by receptor cells. These all contain special sodium channels that are not voltage-gated, but instead are gated by the appropriate stimulus (directly or indirectly). For example chemical-gated sodium channels in tongue taste receptor cells open when a certain chemical in food binds to them; mechanically-gated ion channels in the hair cells of the inner ear open when they are distorted by sound vibrations; and so on. In each case the correct stimulus causes the sodium channel to open; which causes sodium ions to flow into the cell; which causes a depolarisation of the membrane potential, which affects the voltage-gated sodium channels nearby and starts an action potential.
How are Nerve Impulses Propagated?
Once an action potential has started it is moved (propagated) along an axon automatically. The local reversal of the membrane potential is detected by the surrounding voltage-gated ion channels, which open when the potential changes enough.
The ion channels have two other features that help the nerve impulse work effectively:
How Fast are Nerve Impulses?
Action potentials can travel along axons at speeds of 0.1-100 m/s. This means that nerve impulses can get from one part of a body to another in a few milliseconds, which allows for fast responses to stimuli. (Impulses are much slower than electrical currents in wires, which travel at close to the speed of light, 3x108 m/s.) The speed is affected by 3 factors:
The junction between two neurones is called a synapse. An action potential cannot cross the synaptic cleft between neurones, and instead the nerve impulse is carried by chemicals called neurotransmitters. These chemicals are made by the cell that is sending the impulse (the pre-synaptic neurone) and stored in synaptic vesicles at the end of the axon. The cell that is receiving the nerve impulse (the post-synaptic neurone) has chemical-gated ion channels in its membrane, called neuroreceptors. These have specific binding sites for the neurotransmitters.
1. At the end of the pre-synaptic neurone there are voltage-gated calcium channels. When an action potential reaches the synapse these channels open, causing calcium ions to flow into the cell.
2. These calcium ions cause the synaptic vesicles to fuse with the cell membrane, releasing their contents (the neurotransmitter chemicals) by exocytosis.
3. The neurotransmitters diffuse across the synaptic cleft.
4. The neurotransmitter binds to the neuroreceptors in the post-synaptic membrane, causing the channels to open. In the example shown these are sodium channels, so sodium ions flow in.
5. This causes a depolarisation of the post-synaptic cell membrane, which may initiate an action potential.
6. The neurotransmitter is broken down by a specific enzyme in the synaptic cleft; for example the enzyme acetylcholinesterase breaks down the neurotransmitter acetylcholine. The breakdown products are absorbed by the pre-synaptic neurone by endocytosis and used to re-synthesise more neurotransmitter, using energy from the mitochondria. This stops the synapse being permanently on.
Different Types of Synapse
The human nervous system uses a number of different neurotransmitter and neuroreceptors, and they don’t all work in the same way. We can group synapses into 5 types:
1. Excitatory Ion Channel Synapses.
These synapses have neuroreceptors that are sodium channels. When the channels open, positive ions flow in, causing a local depolarisation and making an action potential more likely. This was the kind of synapse described above. Typical neurotransmitters are acetylcholine, glutamate or aspartate.
2. Inhibitory Ion Channel Synapses.
These synapses have neuroreceptors that are chloride channels. When the channels open, negative ions flow in causing a local hyperpolarisation and making an action potential less likely. So with these synapses an impulse in one neurone can inhibit an impulse in the next. Typical neurotransmitters are glycine or GABA.
3. Non Channel Synapses.
These synapses have neuroreceptors that are not channels at all, but instead are membrane-bound enzymes. When activated by the neurotransmitter, they catalyse the production of a "messenger chemical" inside the cell, which in turn can affect many aspects of the cell’s metabolism. In particular they can alter the number and sensitivity of the ion channel receptors in the same cell. These synapses are involved in slow and long-lasting responses like learning and memory. Typical neurotransmitters are adrenaline, noradrenaline (NB adrenaline is called epinephrine in America), dopamine, serotonin, endorphin, angiotensin, and acetylcholine.
4. Neuromuscular Junctions.
These are the synapses formed between motor neurones and muscle cells. They always use the neurotransmitter acetylcholine, and are always excitatory. We shall look at these when we do muscles. Motor neurones also form specialised synapses with secretory cells.
5. Electrical Synapses.
In these synapses the membranes of the two cells actually touch, and they share proteins. This allows the action potential to pass directly from one membrane to the next. They are very fast, but are quite rare, found only in the heart and the eye.
One neurone can have thousands of synapses on its body and dendrons. So it has many inputs, but only one output. The output through the axon is called the Grand Postsynaptic Potential (GPP) and is the sum of all the excitatory and inhibitory potentials from all that cell’s synapses. If there are more excitatory potentials than inhibitory ones then there will be a GPP, and the neurone will "fire", but if there are more inhibitory potentials than excitatory ones then there will not be a GPP and the neurone will not fire.
This summation is the basis of the processing power in the nervous system. Neurones (especially interneurones) are a bit like logic gates in a computer, where the output depends on the state of one or more inputs. By connecting enough logic gates together you can make a computer, and by connecting enough neurones together to can make a nervous system, including a human brain.
Almost all drugs taken by humans (medicinal and recreational) affect the nervous system. From our understanding of the human nervous system we can understand how many common drugs work. Drugs can affect the nervous system in various ways, shown in this table:
Mimic a neurotransmitter
Stimulate the release of a neurotransmitter
Open a neuroreceptor channel
Block a neuroreceptor channel
Inhibit the breakdown enzyme
Inhibit the Na+K+ATPase pump
Block the Na+ or K+ channels
Switch on a synapse
Switch on a synapse
Switch on a synapse
Switch off a synapse
Switch on a synapse
Stop action potentials
Stop action potentials
Drugs that stimulate a nervous system are called agonists, and those that inhibit a system are called antagonists. By designing drugs to affect specific neurotransmitters or neuroreceptors, drugs can be targeted at different parts of the nervous system. The following paragraph describe the action of some common drugs. You do not need to know any of this, but you should be able to understand how they work.
1. Drugs acting on the central nervous system
In the reticular activating system (RAS) in the brain stem noradrenaline receptors are excitatory and cause wakefulness, while GABA receptors are inhibitory and cause drowsiness. Caffeine (in coffee, cocoa and cola), theophylline (in tea), amphetamines, ecstasy (MDMA) and cocaine all promote the release of noradrenaline in RAS, so are stimulants. Antidepressant drugs, such as the tricyclics, inhibit the breakdown and absorption of noradrenaline, so extending its effect. Alcohol, benzodiazepines (e.g. mogadon, valium, librium), barbiturates, and marijuana all activate GABA receptors, causing more inhibition of RAS and so are tranquillisers, sedatives and depressants. The narcotics or opioid group of drugs, which include morphine, codeine, opium, methadone and diamorphine (heroin), all block opiate receptors, blocking transmission of pain signals in the brain and spinal chord. The brain’s natural endorphins appear to have a similar action.
The brain neurotransmitter dopamine has a number of roles, including muscle control, pain inhibition and general stimulation. Some psychosis disorders such as schizophrenia and manic depression are caused by an excess of dopamine, and antipsychotic drugs are used to block the dopamine receptors and so reduce its effects. Parkinson’s disease (shaking of head and limbs) is caused by too little dopamine compared to acetylcholine production in the midbrain. The balance can be restored with levodopa, which mimics dopamine, or with anticholinergic drugs (such as procyclidine), which block the muscarinic acetylcholine receptors.
Tetrodotoxin (from the Japanese puffer fish) blocks voltage-gated sodium channels, while tetraethylamonium blocks the voltage-gated potassium channel. Both are powerful nerve poisons. General anaesthetics temporarily inhibit the sodium channels. Strychnine blocks glycine receptors in the brain, causing muscle convulsions and death.
2. Drugs acting on the somatic nervous system
Curare and abungarotoxin (both snake venoms) block the nicotinic acetylcholine receptors in the somatic nervous system, and so relax skeletal muscle. Myasthenia gravis (a weakening of the muscles in the face and throat caused by inactive nicotinic acetylcholine receptors) is treated by the drug neostigmine, which inhibits acetylcholinesterase, so increasing the amount of acetylcholine at the neuromuscular junction. Nerve gas and organophosphate insecticides (DDT) inhibit acetylcholinesterase, so nicotinic acetylcholine receptors are always active, causing muscle spasms and death. Damaged tissues release prostaglandins, which stimulate pain neurones (amongst other things). The non-narcotic analgesics such as aspirin, paracetamol and ibuprofen block prostaglandin production at source of pain, while paracetamol has a similar effect in the brain. Local anaesthetics such as procaine block all sensory and motor synapses at the site of application.
3. Drugs acting on the autonomic nervous system
Sympathetic agonists like salbutamol and isoprenaline, activate the adrenergic receptors in the sympathetic system, encouraging smooth muscle relaxation, and are used as bronchodilators in the treatment of asthma. Sympathetic antagonists like the beta blockers block the noradrenaline receptors in the sympathetic nervous system. They cause dilation of blood vessels in the treatment of high blood pressure and migraines, and reduce heartbeat rate in the treatment of angina and abnormal heart rhythms. Parasympathetic antagonists like atropine (from the deadly nightshade belladonna) inhibit the muscarinic acetylcholine receptors in parasympathetic system, and are used as eye drops to relax the ciliary muscles in the eye.
The human brain is the site of the major coordination in the nervous system. It contains around 1010 neurones, each making thousands of connections to others, so the number of pathways through the brain is vast. Different regions of the brain can be identified by their appearance, and it turns out that each region has a different role.
These regions of the brain are all involved in involuntary functions, and are connected to the autonomic nervous system. A large part of the brain’s processing concerns these routine processes that keep the body working. By contrast, the upper half of the brain, the cerebrum, is responsible for all voluntary activities, and is connected to the somatic nervous system. The cerebrum is divided down the middle by a deep cleft into two cerebral hemispheres. The two halves are quite separate except for the corpus callosum, a bundle of 200 million neurones which run between the two halves. The inside contains fluid and only the outer few mm of the cerebral hemispheres contains neurones, and this is called the cerebral cortex (or just cortex). The cortex is highly folded and so has a large surface area. The cortex is the most complicated, fascinating and least-understood part of the brain.
The Cerebral Cortex
Various techniques have been used to investigate the functions of different parts of the brain. Patients with injuries to specific parts of the brain (such as strike victims) can be studies to see which functions are altered. The brain itself has no pain receptors, so during an operation on the brain, it can be studied while the patient is alert. Different parts of the brain can be stimulated electrically to see which muscles in the body respond, or conversely different parts of the body can be stimulated to see which regions of the brain show electrical activity. More recently, the non-invasive technique of magnetic resonance imaging (MRI) has been used to study brain activity of a subject without an operation.
Studies like these have shown that the various functions of the cortex are localised into discrete areas. These areas can be split into three groups:
Some of these areas are shown on this map of the surface of the cerebral cortex.
Motor and Sensory Areas
The main motor area controls the main skeletal muscles of the body, and the main sensory area receives input from the various skin receptors all over the body. These two areas are duplicated on the two cerebral hemispheres, but they control the opposite side of the body. So the main sensory and motor areas of the left cerebral hemisphere are linked to the right side of the body, and those of the right cerebral hemisphere are linked to the left side of the body.
These two areas have been studied in great detail, and diagrams can be drawn mapping the part of the cortex to the corresponding part of the body. Such a map (also called a homunculus or "little man") can be drawn for the main sensory and motor areas:
The sensory and motor maps are similar, though not identical, and they show that regions of the body with many sensory (or motor) neurones have correspondingly large areas of the cortex linked to them. So the lips occupy a larger region of the sensory cortex than the shoulder, because they have many more sensory neurones. Similarly, the tongue occupies a larger region of the motor cortex than the trunk because it has more motor neurones controlling its muscles.
While the jobs of the sensory and motor areas are reasonably well defined, the jobs of the association areas are far less clear. The association areas contain multiple copies of the sensory maps and they change as the sensory maps change. These copies are used to compare (or associate) sensory input with previous experiences, and so make decisions. They are therefore involved in advanced skills such as visual recognition, language understanding (aural and read), speech, writing and memory retrieval. The frontal lobes are particularly large in humans, and thought to be responsible for such higher functions as abstract thought, personality and emotion. We’ll look briefly at two examples of advanced processing: comprehension and visual processing.
This flow diagram shows how different areas of the cortex work together during a school lesson when a student has to understand the teacher’s written and spoken word, write notes, and answer questions.
Unlike the sensory and motor areas, the association areas are not duplicated in the two hemispheres. Association areas in the two hemispheres seem to supervise different skills.
These distributions apply to most right-handers, and are often reversed for left-handers. However, even this generalisation is often not true. For example, Broca’s area, the speech association areas is quite well-defined and well studied. 95% of right-handers have Broca’s area in their left hemisphere while 5% have it in their right. 70% of left-handers have Broca’s area in their left hemisphere, 15 in their right, and 15% in both hemispheres! Any reference to "right brain skills" or "left brain skills" should be taken with a large dose of scepticism.
The visual sensory area is at the back of the brain and receives sensory input from the optic nerves. Some of the neurones from each optic nerve cross over in the optic chiasma in the middle of the brain, so that neurones from the left half of the retinas of both eyes go to the visual sensory area in the left hemisphere and neurones from the right half of the retinas of both eyes go to the visual sensory area in the right hemisphere. Thus the two hemispheres see slightly different images from opposite side of the visual field, and the differences can be used to help judge distance.
The mechanism of visual processing is complex and not well understood, but it is clear so far that the brain definitely does not work like a digital camera, by forming an image of pixels. Instead it seems to recognise shapes. The neurones in the visual cortex are arranged in 6 layers, each with a different hierarchical function in processing the visual information. The first layer recognises sloping lines, the second recognises complete shapes, the third recognises moving lines, and so on.