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The nervous system is made up of the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS includes the brain and spinal cord. Nerves distal to this system form the PNS. Peripheral nerves that conduct signals from the peripheries to the CNS can be described as afferent (sensory) nerves. Efferent (motor) nerves transmit signals from the CNS to target organs/tissues.
The nervous system contains a range of cells. The cells that transmit signals are called neurones. The neuron has a cell body, from which a web of short projections called dendrites originate, which can then interact with other cells. Dendrites increase the available surface area for other neurones to interface with. A motor nerve cell (neuron) can connect to over 10,000 other neurons through connections between the dendrites and the 'pre-synaptic' terminals of other neurones overlying them. The cell has one long projection called the axon, which transmits the signal. The CNS contains two types of tissue, grey and white matter. Grey matter is densely packed with nerve cell bodies and white matter contains the nerve axons. Some nerves are sheathed in a substance called myelin. Myelin is created by oligodendrocytes in the CNS and Schwann cells in the PNS. Signals jump between gaps in the myelin called 'nodes of Ranvier'. This means that only the nodes along the neuron depolarise, rather than the whole length of the neurone. This speeds the transmission of the signal along the neurone.1
The nervous system as a whole, can be further sub-divided into somatic and autonomic nervous systems. The somatic nervous system supplies the skin and musculoskeletal system. It initiates and senses voluntary movement. The autonomic system innervates the viscera, including internal organs, blood vessels and smooth muscle. The somatic and autonomic nervous systems both have components in the CNS and PNS. There are also areas of overlap between the somatic and autonomic nervous systems. The autonomic nervous system is involved in many 'automatic' body functions, such as regulating digestion of food, heart rate and blood vessel dilatation/constriction.
Transmission of nervous system signals occurs through the conduction of electric signals called 'action potentials' along the axon of the nerve. An action potential is a change in voltage across the membrane of the nerve using ion channels. Sodium concentration is higher outside the cell and potassium concentration is higher inside the cell. An influx of extra-cellular sodium through voltagegated ion channels causes depolarisation, these channels then close. Repolarisation occurs as potassium channels open, allowing potassium to exit the cell, diffusing down the concentration gradient. These signals are 'digital', they are all or nothing. Different nerves in the same system may require different levels of stimuli to cause an action potential. This allows a graded response to a stimulus.
Nerve signals (action potentials) transfer from one to another across gaps called synapses, this occurs when a signal is transferred from the CNS to the PNS and within the PNS.
The synapse
The end of the nerve (the terminal button) contains preformed vesicles of substances called neurotransmitters. The arrival of the action potential causes voltage dependent calcium ion channels to open, the influx of calcium initiates the fusion of the vesicles containing neurotransmitter to the pre-synaptic membrane. The vesicles empty their contents into the synaptic cleft (the space between the two neurones). The neurotransmitter diffuses across the synaptic cleft. The signal is detected by receptors on the post-synaptic membrane. Voltage-dependent ion channels are opened, initiating an action potential in the post-synaptic neuron.2 Some neurones generate an excitatory signal and some an inhibitory signal. The signal is terminated by the breakdown and or reabsorption of the neurotransmitter by enzymes in the synaptic cleft.
The broad principles of the function of these junctions are similar across the nervous system. Different parts of the nervous system use different substances for signal transduction. Common neurotransmitters include acetylcholine (Ach), amines, amino acids and peptide chains. Acetylcholine is a common excitatory neurotransmitter found in the CNS. It has an important role in the somatic nervous system, as it transmits signals from the nerve to the muscle at the neuro-muscular junction. Amines include a range of transmitters, catecholamines (noradrenaline and adrenaline), serotonin and histamine. Catecholamines are important autonomic neurotransmitters. They have a common synthetic pathway. This pathway is a common target for pharmacotherapy, particularly in the treatment of depression and psychosis. Tyrosine is metabolised to L-dopa and then to dopamine. Dopamine can be metabolised into noradrenaline (norepinephrine) and adrenaline (epinephrine). Noradrenaline and adrenaline are used as neurotransmitters. They are broken down by mono-aminoxidase in the pre-synaptic membrane or catechol-O-methyl transferase in the post-synaptic neuron.3
Amino acids are key inhibitory and excitatory neurotransmitters. Glutamate is converted to GABA (gamma-aminobutyric acid) and is a CNS inhibitor. Glycine inhibits spinal cord motorneurones. Glutamate and aspartate act as excitatory neurotransmitters.4
There are a range of peptides (short amino acid chains) that may be involved in neuron signalling, such as substance P in pain. Further research is increasing our understanding of the complex use of a combination of inhibitory and excitatory signalling. Some neurones act on the pre-synaptic membrane to modify the signal. The principle of adjusting the signal strengths is called neuromodulation. This improves the ability of the nervous system to provide a graded response to stimuli.
Classification of the autonomic nervous system
As previously mentioned the autonomic nervous system is responsible for the control of subtle responses to stimuli that are to some degree automatic. The autonomic nervous system can be further subdivided into the sympathetic and parasympathetic nervous systems. Both sympathetic and parasympathetic nervous systems involve features of the CNS and PNS. The sympathetic and parasympathetic systems are broadly antagonistic in their function.
Both have a similar connection between the CNS and target cell. The nerves synapse in a junction (ganglion) outside the CNS. The nerve leading to the pre-synaptic membrane is a pre-ganglionic fibre in t. The nerve beginning at the post-synaptic membrane is the post-ganglionic fibre. Synapse transmission is mediated by the Ach at the ganglion in both sub-divisions of the autonomic system. Signal transmission between the post-ganglionic fibre and target is mediated by noradrenaline in the sympathetic nervous system and by Ach in the parasympathetic nervous system.2
Sympathetic nervous system
The sympathetic nervous system is stimulated in response to stress. This leads to an increase in heart rate, blood pressure and blood flow to skeletal muscle. This also leads to a decrease in blood flow to organs not necessary for a 'fight or flight' response, gastro-intestinal and skin blood vessels vasoconstrict. The parasympathetic nervous system is more active in a state of 'rest', for example in the digestion of food. Blood flow to the gut increases and gut motility is stimulated.
The cell bodies of the pre-ganglionic sympathetic fibres can be found in the grey matter of the spinal cord between the first thoracic vertebra (T1) and the third lumbar vertebra (L3), the axons run parallel to the vertebral column in the 'para-vertebral sympathetic column'. Many ganglions can be found within this chain. Post-ganglionic fibres are long and run from the sympathetic column to the target tissue.
Receptors in the post-ganglionic sympathetic system respond to noradrenaline, they are sub-divided into alpha and beta adrenoceptors. They have different effects and each has a different pattern of distribution. Alpha and beta receptors are common drug targets, including in hypertension ('beta-blockers'), asthma and the eye.5
Alpha receptor stimulation causes vasoconstriction and contraction of intestinal sphincters. Beta adrenoceptor stimulates relaxation of smooth muscle, this causes vasodilatation, relaxation of airways, bladder and intestinal smooth muscle. Paradoxically, stimulating beta adrenoceptors in the heart causes an increase in heart rate and increased cardiac muscle contraction (is positively inotropic).
Parasympathetic nervous system
Pregangionicneurones arise from nuclei in the brain or the sacrum (base) of the spinal cord. They exit the CNS from cranial or pelvic splanchlic nerves. The pre-ganglionic fibres are much longer and consequently the post-ganglionic fibres are shorter, nearer the target organ.
The parasympathetic nervous system works uses exclusively Ach as its neurotransmitter. Ach receptors can be divided into those stimulated by the drug muscarine (muscarinic receptors) and nicotinic acid (nicotinic receptors). Muscarinic receptors are found at the post-ganglionic synapse. Nicotinic receptors are found in the ganglion synapse. The parasympathetic system is not as widely distributed as the sympathetic system. Effects of the parasympathetic stimulation include decreased heart rate, intestinal contraction, contraction of bladder, bowel and airway smooth muscle.
When both components are working a balance is achieved. An example can be seen in the control of heart rate. Resting heart rate is between 60-100 beats per minute. Removal of sympathetic stimulation of heart rate means it falls to. Removal of parasympathetic stimulation of heart rate means it rises to.
Autonomic innervation of the eye
The eye is innervated by both sympathetic and parasympathetic fibres of the eye. Sympathetic innervation of the eye arises from the level of T1 in the spinal cord. The nerve fibres enter the sympathetic chains and ascend to the superior cervical ganglion leaving the CNS. The post-ganglionic fibres initially travel with the carotid artery ascending towards the eye. Sympathetic fibres innervate radial fibres of the iris, the superior tarsal muscle (part of levatorpalpebrae) and some innervation to the ciliary muscle. The sympathetic chains also innervate blood vessel smooth muscle, sweat and salivary glands.6 These features are important in detecting conditions such as Horner's syndrome. Sympathetic stimulation leads to the dilation of the pupil raising of the upper eyelid and control of mucus, saliva and sweat production.
Parasympathetic nerves arise from the 'Edinger-Westphal' nucleus. This is described as the visceral nucleus of the third cranial nerve (ocular-motor nerve). Parasympathetic fibres travel with those from cranial nerves III, VII, IX and X ocular-motor fibres and exit the CNS to form the ciliary ganglion. This lies immediately posterior to the eye. Post-ganglionic fibres form the ciliary nerve and innvervate the ciliary muscle and the sphincter pupillae. Stimulation of the parasympathetic fibres leads to ciliary muscle contraction, the ciliary body is then closer to the eye. There is less tension on the lens allowing it to become more convex in shape. This allows greater focusing power at short distance.
Pupillary innervation
An increase in available light leads to the stimulation of the papillary light reflex, the retina detects the increase in light, passing the signal along the optic nerve (second cranial nerve) to the pretectal nucleus, on to the Edinger-Westphal nucleus. Parasympathetic fibres from this nucleus pass back to the eye initiating miosis. A lack of available light and stimulation of the sympathetic system leads to mydriasis. Radial smooth muscle contracts causing papillary dilatation.6
References
- McGeown G. Masters of Medicine: Physiology.
- Snell R. Organisation of the autonomic nervous system. Clinical Anatomy, 6th edition. (2006), Lippincott and Williams.p393-402.
- Dopamine pathway.
- Reference re: GABA.
- Pharmacology of alpha and beta adrenoceptors.
- Guyton A and Hall J. Human physiology and mechanisms of disease, 6th edition (1997), p424-425. WB Saunders Company.