Autonomic nervous system
| Bill Blessing and Ian Gibbins (2008), Scholarpedia, 3(7):2787. | doi:10.4249/scholarpedia.2787 | revision #150512 [link to/cite this article] |
The term autonomic nervous system (ANS) refers to collections of motor neurons (ganglia) situated in the head, neck, thorax, abdomen, and pelvis, and to the axonal processes of these neurons (Fig.<ref>F1</ref>). Autonomic pathways, somatic motor pathways to skeletal muscle, and neuroendocrine pathways, and comprise the three motor outflows from the CNS. There are also central components of the ANS, within the brain and spinal cord, including preganglionic neurons in the central nervous system that project to motor neurons in autonomic ganglia. Thus, autonomic motor neurons are clearly distinguished from somatic motor neurons that project from the central nervous system directly to skeletal muscles, without any intervening ganglia.
Axonal processes of these final motor neurons (post-ganglionic axons) innervate organs and tissues throughout the body (eyes, salivary glands, heart, stomach, urinary bladder, blood vessels, etc). Complex autonomic ganglia in the walls of the stomach and small intestine are separately classified as the enteric nervous system.
History of the definition and functional conception of the ANS
Emotional feeling has traditionally been seen as distinct from rational thought. The brain, locked away in its bony case, was conceived as responsible for rational thought and for ideas that direct behavioral interactions with the external environment. Emotions, visceral rather than rational, were linked with the functions of the internal bodily organs. We have “gut feelings”, the heart is the “seat of love” and we “vent our spleen”. Bichat (1771-1802) divided life into two distinct forms, one (relational life) governed by the brain, and the other (organic life) by the abdominal ganglia. Organic life was seen as connected with the passions and independent of education, governed as it is by independently functioning abdominal ganglia, a chain of “little brains”. Phillipe Pinel, one of the founders of modern psychiatry, and Bichat’s teacher, even considered mental disease to be caused by abnormal function of these ganglia.
Langley (1852-1925) coined the term autonomic nervous system. Langley noted the absence of sensory (afferent) nerve cell bodies in autonomic ganglia and defined the ANS as a purely motor system. He nevertheless continued the tradition whereby the ANS is seen as functioning in its own right, with independence from the CNS. It should be noted that Langley did not completely adhere to this simplification. In his introduction to the ANS (1903) he wrote that it is possible to “consider as afferent autonomic fibres those which give rise to reflexes in autonomic tissues, and which are incapable of directly giving rise to sensation”. Moreover, the discovery of primary afferent neurons that are part of the ANS, but lie entirely outside the CNS, and make no direct connection with the CNS, make it difficult to conceive of the ANS as an entirely efferent system (Furness 2006; see further below).
Modern experiments have shown that neurons in autonomic ganglia do not have inbuilt discharge patterns sufficiently integrated to regulate physiological functions, with the possible exception of neurons within the enteric nervous system of the small and large intestines. The classic description of hexamethonium man summarizes the state of an individual after drug-mediated separation of the ANS from functional control by the brain. Similarly, when brain control of spinal autonomic preganglionic neurons is removed (as in quadriplegia), cardiovascular, bowel and bladder functions are profoundly impaired. Thus the ANS is best seen as one of the outflows whereby the CNS controls bodily organs, so that “peripheral autonomic pathways” is a better term, but “autonomic nervous system” is well-established.
ANS pathways are divided into sympathetic and parasympathetic (around the sympathetic) divisions and enteric plexuses. Preganglionic cell bodies for the sympathetic outflow are in the thoracic spinal cord. Preganglionic cell bodies for the parasympathetic outflow are in the brainstem (cranial) and in the sacral spinal cord (sacral). The idea that the divisions oppose each other is a misleading simplification. Neither division is ever activated in its entirety. Rather, each division consists of a series of discrete functional pathways that may be activated from the CNS either independently or in patterns, according to the particular requirement of the particular daily activity that is contributing to bodily homeostasis. The primacy of integrative brain control of all bodily functions was recognized by Walter Cannon, but his idea that the brain activates sympathetic nerves diffusely and non-specifically during bodily emergencies (“fight or flight reaction”) is an over simplification. Different emergency states require different patterns of autonomic activity, and normal daily life (apart from emergencies) also requires patterned autonomic activity. The individual functions as a whole: there is just one nervous system.
Sensory information (visceral afferent information) relevant to autonomic control (eg degree of bladder distention or level of blood pressure) travels in visceral afferent nerves and enters the CNS via spinal afferent pathways, or via vagal or glossopharyngeal afferents that project into the lower brainstem (see white-filled black arrows in Fig. <ref>F1</ref>).
Autonomic Neurotransmitters
All preganglionic autonomic neurons, both sympathetic and parasymapthetic use acetylcholine (ACh) as their fast excitatory transmitter. In the ganglia, ACh acts on a subclass of nicotinic receptors, distinct from nicotinic receptors at the skeletal muscle neuromuscular junction. Many preganglionic autonomic neurons also contain neuropeptides (co-transmitters) that mediate slow excitatory post-synaptic potentials, facilitating cholinergic transmission. Most sympathetic final motor neurons utilise noradrenaline (norepinephrine) as their primary transmitter, together with co-transmitters such as ATP and peptides such as neuropeptide Y (NPY) and galanin. Some sympathetic final motor neurons (especially those innervating sweat glands) use ACh as their main non-peptide transmitter. Parasympathetic final motor neurons pathways usually use ACh, nitric oxide, or both as non-peptide transmitters, as well as a wide range of co-transmitter peptides including vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), somatostatin and opioid peptides. No parasympathetic neurons use noradrenaline as a transmitter. ACh is also a major transmitter utilised by enteric neurons. Other enteric neurotransmitters are substance P, VIP, enkephalin, 5-HT and ATP. Axons of final motor neurons ramify throughout their target tissues, typically smooth muscle, secretory tissue or cardiac muscle. Axon terminals are specialized for neurotransmission, but they usually lack the structures characteristic of conventional synaptic contacts. A number of target tissues are innervated by both sympathetic and parasympathetic nerves (eg the heart, the iris muscle, some salivary glands, the gastrointestinal tract and pelvic organs).
Cranial parasympathetic pathways
The cranial parasympathetic pathways project to a wide variety of targets in the head, neck, thorax and abdomen (Fig. <ref>F1</ref>). The pathways are associated with four of the cranial nerves: the oculomotor (III), facial (VII), glossopharyngeal (IX) and the vagus (X). Most final motor neurons in these cranial autonomic pathways are in four pairs of major ganglia: the ciliary ganglia (III), sphenopalatine or pterygopalatine ganglia (VII), submandibular ganglia (VII), and otic ganglia (IX). The final motor neurons of the vagal autonomic pathways lie mostly in microganglia located near or within the target organs.
The major target of cranial parasympathetic pathways are secretory glands associated with the eye (tears), mouth (saliva) and nose (mucus). They stimulate the secretion of watery fluid, often with a concomitant vasodilation. Parasympathetic pathways also have a critical role in focussing the eye and regulating pupil diameter. Blood vessels in the brain also receive a parasympathetic vasodilator innervation, but the actual physiological function of these nerves is not well understood. The vagus nerve innervates microganglia in the neck, thorax and abdomen, including the airways, heart, thyroid, pancreas, gall bladder and the upper gastrointestinal tract. Consequently, the vagus nerve has a vast array of actions. It alters resistance to airflow and increases mucus secretion from the upper respiratory tract; it slows the heart; it stimulates secretion of digestive enzymes and bicarbonate from the pancreas; it either increases or decreases both secretory activity and smooth muscle contractility in the stomach. Some parasympathetic pathways tend to be tonically active (eg vagal pathways that keep heart rate low when we are not exercising) whereas others are activated only when required, eg salivary secretion during eating; relaxation of gastric smooth muscle; or near focus of the eyes when reading.
Sympathetic Pathways
Neurons of the sympathetic division of the autonomic nervous system are aggregated into two main collections of ganglia: the paravertebral ganglia, which form the sympathetic chain each side of the vertebral column, and the prevertebral ganglia lying around the origins of the coeliac and mesenteric arteries (Fig. <ref>F1</ref>). Sympathetic neurons project to most tissues of the body, commonly reaching them by traveling with major nerves containing predominantly sensory and somatic motor nerve fibers.
Sympathetic pathways have a diverse range of activities. Many are active nearly all the time, eg, vasoconstrictor pathways to the muscles that maintain central blood pressure, vasoconstrictor pathways to the skin that help prevent excessive heat loss, or prevertebral pathways to the gastrointestinal tract that help prevent excessive water loss from the gut. Other sympathetic pathways are activated only on demand, eg those to that increase heart rate during exercise; sudomotor neurons stimulating sweating during high body temperature; or those stimulating ejaculation during sexual activity. In some circumstances, sympathetic and parasympathetic pathways to a target tissue are co-activated eg sympathetic pathways to the salivary glands are co-activated with parasympathetic pathways when we eat something potentially noxious, such as hot chillies. The sympathetic co-activation results in the production of a thicker, more viscous saliva.
Sympathetic pathways normally are never activated all at once. Despite the widespread belief that they are only activated during stressful situations, on-going activity of specific sympathetic pathways are essential for our day-to-day health and well-being. Even when we are faced with extreme stress, only a subset of sympathetic pathways will be involved.
Pelvic autonomic pathways
Regulation of the activity of many pelvic organs requires coordinated control via both sympathetic and sacral parasympathetic pathways, often in association with the relevant somatic motor pathways. Indeed, many of the ganglia in pelvic pathways contain mixtures of neurons, some of which receive preganglionic inputs from lumbar spinal levels (by definition, sympathetic) and others of which receive preganglionic input from sacral spinal levels (by definition, parasympathetic). Some individual neurons receive convergent inputs from both lumbar and sacral preganglionic neurons, and there may be considered to lie in both sympathetic and parasympathetic pathways.
Control of bladder function requires sympathetic and somatic activity to relax the bladder wall and keep sphincters closed during continence. In contrast, micturition (urination) involves parasympathetic activation to contract the bladder wall and relax the sphincters, along with somatic motor pathways to increase intra-abdominal pressure. During sexual activity, erection requires coordinated activity of parasympathetic and somatic pathways, whilst ejaculation is the result of coordinated sympathetic and somatic motor activity.
Brain and spinal cord pathways regulating autonomic outflow
Preganglionic neurons for parasympathetic and sympathetic autonomic outflow are located in the brainstem and in regions of the spinal cord (Fig. <ref>F1</ref>). Brain centres controlling these preganglionic neurons have been defined by physiological studies and by a neuroanatomical technique in which a live virus, with affinity for autonomic nerves, is injected into a bodily organ, eg the wall of the stomach, the bladder or one of the salivary glands in experimental animals. The virus is transported to the autonomic nerve cell body in the ganglion. Here it replicates, spreads trans-synaptically and is then transported back into the CNS, to the preganglionic neurons, and then to neurons with direct axonal inputs to preganglionic neurons. For the sympathetic outflow, brain regions containing premotor neurons include medulla oblongata, pons and hypothalamus. Many of these premotor neurons synthesize a monoamine (noradrenaline, adrenaline, dopamine or serotonin). “Higher order” brain regions relevant to control of autonomic function are then labeled in the subsequent waves of spreading viral infection.
Afferent inputs to autonomic pathways
We have defined autonomic pathways as one of the major motor outputs of the nervous system. However, not all autonomic neurons have a motor function. In particular, there are significant populations of neurons within the enteric nervous system that have a primary sensory function. Comprising 25% or more of the myenteric and submucosal plexuses, these neurons have a characteristic morphology and electrophysiological properties. Different populations of enteric sensory neurons respond to various mechanical or chemical stimuli and form the afferent limbs of reflex circuits in the enteric plexuses that regulate intestinal motility and secretion. In addition to these sensory neurons, the enteric plexuses also contain several populations of interneurons, each of which has a characteristic projection and neurochemical profile.
While it is sometimes proposed that there are “autonomic afferents” in addition to those within the enteric plexuses, autonomic motor activity can be activated by a wide variety of sensory or centrally generated inputs, none of which is necessarily specific for autonomic activity alone. The best way to illustrate this idea is by a set of examples, all of which are well understood, albeit commonly overlooked.
Visceral afferents
Probably all the viscera are innervated by unmyelinated sensory neurons (visceral afferents) that respond to a range of noxious stimuli, such as tissue inflammation, low pH, or ischaemia. When activated, they may produce a conscious perception of pain originating in the organ. Because the peripheral fibres of these afferent neurons often run in the same nerve trunks as sympathetic motor fibres to the same target tissues, they are sometimes referred to as “sympathetic afferents”. However, although stimulation of these sensory neurons can result in changes of sympathetic activity (eg vasomotor responses), they also lead to somatic motor activity, such as spasm of the abdominal muscles or increase respiratory rate using the diaphragm and other respiratory muscles.
Nevertheless, there are various sets of sensory neurons that respond to changes of physiological variables of which we have little conscious awareness and that generate changes in autonomic activity. Amongst these are the baroreceptors, which measure blood pressure via specialised sensory endings in the carotid arteries, just before they enter the skull. Changes in baroreceptor activity lead to altered sympathetic motor outflow to the cardiovascular system, with the overall aim of maintaining adequate blood flow to the brain under a wide range of circumstances, ranging from simply standing up quickly, to coping with blood loss after an injury.
Control of accommodation and pupil diameter
Accommodation refers to the ability of the eye to focus on nearby objects by changing the shape of the lens. This is a parasympathetic motor function that is largely under conscious control, with sensory input arising from the visual system. Changes in pupil diameter regulate the amount of light reaching the retina and allow the eye to adapt to varying levels of ambient light. Pupil diameter is regulated by a combination of parasympathetic and sympathetic innervation of smooth muscle in the iris, in response to the global level of incident light. The overall level of illumination is detected by a special set of photosensitive ganglion cells in the retina.
Tears in the eyes
If we are sad or upset or, perhaps, incredibly relieved or deliriously happy, we may cry. Lacrimation, the production of tears, is a pure parasympathetic motor activity. Most of the time, there is a low level of tear production that helps keep the cornea clean when we blink. Lacrimation can occur in response to irritation of the eye by mechanical irritation (eg a grain of sand) or chemical irritation (eg a squirt of lemon juice). We also may cry if we receive noxious mechanical stimulation of a nearby part of the face (eg a whack across the bridge of the nose). We may ceven ry in response to a complex visual stimulus, such as a sad scene in a movie. Finally, if we are in a heightened emotional state, we may cry, perhaps in the absence of any immediate external stimulus at all. In all of these situations, the increased parasympathetic activity may be accompanied by characteristic patterns of somatic motor activity such as vocalisations (eg wailing) and facial expressions.
Auditory system input to cardiovascular system and cutaneous thermoregulators
Many types of auditory input can activate sympathetic motor innervation of the heart and peripheral vasculature. For example, a sudden unexpected sound causes an increase in heart rate and vasoconstriction in the skin. On the other hand, a piece of music with special emotional resonance may give “send a shiver down your spine” and “give you goosebumps”. Goosebumps are generated by sympathetic activation of small smooth muscles associated with each hair follicle, an evolutionary remnant from a time when we presumably possessed a much more luxuriant pelage. If we really do shiver in response to the music, we will have generated a somatic motor response as if we were actually feeling cold.
Indeed, if we really do need to raise our body temperature, either because the environment is cold (detected by cutaneous thermoreceptors) or because we have a fever, generated from the thermoregulatory areas of the hypothalamus, we will shiver (a somatic motor response) and reduce blood flow to the skin (a sympathetic response).
Sexual activity
Sexual activity requires coordinated motor activity of parasympathetic, sympathetic and somatic motor pathways. In males, erection is maintained mostly by parasympathetic activity, whilst ejaculation is controlled mostly by sympathetic activity. In both these components, somatic motor activity is required to control muscles of the pelvic floor and the external sphincters, for example, as well as all the various body movements involved in intercourse. As is well known, erection can be elicited either by appropriate cutaneous mechanical stimulation, which activates a special set of cutaneous mechanoreceptors in genital skin, or by psychogenic means.
Feeling nervous
One of the best known but most misinterpreted autonomic motor patterns in the response to stress. Typically this involves an increase in sympathetic activity in selected pathways, such as those to the cardiovascular system, producing increase heart rate, skin blanching and perhaps hypertension, and to the sweat glands, especially those of the face, armpits and hands. This pattern of activity is most commonly entirely psychogenic in origin, although it may be aggravated by a variety of sensory inputs from the visual and auditory systems.
Feeling sick
Perhaps the archetypal “visceral afferents” are those from the gastro-intestinal tract. There are many different functional classes of these sensory nerves. Some respond to distention of the gut; others detect changes in the contents of the gut; yet others respond to inflammation or damage to the gut wall. Almost certainly, we are consciously aware of only some of this sensory input to the central nervous system and we may have little if any conscious control of the motor outputs. Such outputs might involve parasympathetic or sympathetic regulation of gut motility, for example.
In some circumstances, such as food poisoning, not only does stimulation of gut afferents generate autonomic motor activity, but it also generates coordinated somatic motor activity. If we are really sick, we may vomit, which involves activation of somatic motor pathways to the abdominal muscles, as well as muscles of the pharynx. Autonomic pathways include those regulating contraction and relaxation of the stomach and oesophagus, saliva secretion from the main salivary glands, and probably the cardiovascular system as well. Intriguingly, we can generate the same coordinated set of responses entirely from central pathways, such as when we see an event or scene that is so disgusting, it literally makes us sick, or if we are “sick with worry”. It is now known that nausea generated either from the gastrointestinal tract or from a visual stimulus is associated with the activation of very similar central pathways.
References
Ackerknecht, E.H. (1974) The history of the discovery of the vegetative (autonomic) nervous system. Medical History.18: 1-8.
Blessing W.W. (1997) The Lower Brainstem and Bodily Homeostasis. Oxford University Press, New York.
Furness J.B. (2006) Enteric Nervous System. Blackwell Publishing, Oxford.
Furness J.B. (2006) The organisation of the autonomic nervous system: peripheral connections. Autonomic Neuroscience 130, 1-5
Gibbins I.L. (2004) Peripheral Autonomic Pathways. In: Paxinos G, Mai JK, eds. The Human Nervous System. Second edition Amsterdam: Elsevier Academic Press, 134-189.
Jänig W.W. (2006) The Integrative Action of the Autonomic Nervous System: Neurobiology of Homeostasis. Cambridge University Press, Cambridge.
Langley J.N. (1903) The autonomic nervous system. Brain 26, 1-26
Loewy A.D. and Spyer, K.M. (1990) Central Regulation of Autonomic Function. Oxford University Press, New York.
--Blessing 21:53, 25 June 2007 (EDT)
