The autonomic nervous system is the part of the peripheral nervous system that regulates the basic visceral processes needed for the maintenance of normal bodily functions. It operates independently of voluntary control, although certain events, such as stress, fear, sexual excitement, and alterations in the sleep-wake cycle, change the level of autonomic activity.The autonomic system usually is defined as a motor system that innervates three major types of tissue: cardiac muscle, smooth muscle, and glands. However, it also relays visceral sensory information to the central nervous system and processes it so that alterations can be made in the activity of specific autonomic motor outflows, such as those that control the heart, blood vessels, and other visceral organs. It also stimulates the release of certain hormones involved in energy metabolism (e.g., insulin, glucagon, and epinephrine [also called adrenaline]) or cardiovascular functions (e.g., renin and vasopressin). These integrated responses maintain the normal internal environment of the body in an equilibrium state called homeostasis.
The autonomic system consists of two major divisions: the sympathetic nervous system and the parasympathetic nervous system. These often function in antagonistic ways. The motor outflow of both systems is formed by two serially connected sets of neurons. The first set, called preganglionic neurons, originates in the brainstem or the spinal cord, and the second set, called ganglion cells or postganglionic neurons, lies outside the central nervous system in collections of nerve cells called autonomic ganglia. Parasympathetic ganglia tend to lie close to or within the organs or tissues that their neurons innervate, whereas sympathetic ganglia are located at more distant sites from their target organs. Both systems have associated sensory fibres that send feedback into the central nervous system regarding the functional condition of target tissues.
A third division of the autonomic system, the enteric nervous system, consists of a collection of neurons embedded within the wall of the gastrointestinal tract and its derivatives. This system controls gastrointestinal motility and secretion.
SYMPATHETIC NERVOUS SYSTEM
The sympathetic nervous system normally functions to produce localized adjustments (such as sweating as a response to an increase in temperature) and reflex adjustments of the cardiovascular system. Under conditions of stress, however, the entire sympathetic nervous system is activated, producing an immediate, widespread response called the fight-or-flight response. This response is characterized by the release of large quantities of epinephrine from the adrenal gland, an increase in heart rate, an increase in cardiac output, skeletal muscle vasodilation, cutaneous and gastrointestinal vasoconstriction, pupillary dilation, bronchial dilation, and piloerection. The overall effect is to prepare the individual for imminent danger.
Sympathetic preganglionic neurons originate in the lateral horns of the 12 thoracic and the first 2 or 3 lumbar segments of the spinal cord. (For this reason the sympathetic system is sometimes referred to as the thoracolumbar outflow.) The axons of these neurons exit the spinal cord in the ventral roots and then synapse on either sympathetic ganglion cells or specialized cells in the adrenal gland called chromaffin cells.
Sympathetic ganglia
Sympathetic ganglia can be divided into two major groups, paravertebral and prevertebral (or preaortic), on the basis of their location within the body. Paravertebral ganglia generally are located on each side of the vertebrae and are connected to form the sympathetic chain, or trunk. There are usually 21 or 22 pairs of these ganglia—3 in the cervical region, 10 or 11 in the thoracic region, 4 in the lumbar region, and 4 in the sacral region—and a single unpaired ganglion lying in front of the coccyx, called the ganglion impar. The three cervical sympathetic ganglia are the superior cervical ganglion, the middle cervical ganglion, and the cervicothoracic ganglion (also called the stellate ganglion). The superior ganglion innervates viscera of the head, and the middle and stellate ganglia innervate viscera of the neck, thorax (i.e., the bronchi and heart), and upper limbs. The thoracic sympathetic ganglia innervate the trunk region, and the lumbar and sacral
sympathetic ganglia innervate the pelvic floor and lower limbs. All the paravertebral ganglia provide sympathetic innervation to blood vessels in muscle and skin, arrector pili muscles attached to hairs, and sweat glands. The three preaortic ganglia are the celiac, superior mesenteric, and inferior mesenteric. Lying on the anterior surface of the aorta, preaortic ganglia provide axons that are distributed with the three major gastrointestinal arteries arising from the aorta. Thus, the celiac ganglion innervates the stomach, liver, pancreas, and the duodenum, the first part of the small intestine; the superior mesenteric ganglion innervates the small intestine; and the inferior mesenteric ganglion innervates the descending colon, sigmoid colon, rectum, urinary bladder, and sexual organs.
Neurotransmitter and receptors
Upon reaching their target organs by traveling with the blood vessels that supply them, sympathetic fibres terminate as a series of swellings close to the end organ. Because of this anatomical arrangement, autonomic transmission takes place across a junction rather than a synapse. “Presynaptic” sites can be identified because they contain aggregations of synaptic vesicles and membrane thickenings; postjunctional membranes, on the other hand, rarely possess morphological specializations, but they do contain specific receptors for various neurotransmitters. The distance between pre- and postsynaptic elements can be quite large compared with typical synapses. For instance, the gap between cell membranes of a typical chemical synapse is 30–50 nanometres, while in blood vessels the distance is often greater than 100 nanometres or, in some cases, 1–2 micrometres (1,000–2,000 nanometres). Owing to these relatively large gaps between autonomic nerve terminals and their effector cells, neurotransmitters tend to act slowly; they become inactivated rather slowly as well. To compensate for this inefficiency, many effector cells, such as those in smooth and cardiac muscle, are connected by low-resistance pathways that allow for electrotonic coupling of the cells. In this way, if only one cell is activated, multiple cells will respond and work as a group.
At a first approximation, chemical transmission in the sympathetic system appears simple: preganglionic neurons use acetylcholine as a neurotransmitter, whereas most postganglionic neurons utilize norepinephrine (noradrenaline)—with the major exception that postganglionic neurons innervating sweat glands use acetylcholine. On closer inspection, however, neurotransmission is seen to be more complex, because multiple chemicals are released, and each functions as a specific chemical code affecting different receptors on the target cell. In addition, these chemical codes are self-regulatory, in that they act on presynaptic receptors located on their own axon terminals.
The chemical codes are specific to certain tissues. For example, most sympathetic neurons that innervate blood vessels secrete both norepinephrine and neuropeptide Y; sympathetic neurons that innervate the submucosal neural plexus of the gut contain both norepinephrine and somatostatin; and sympathetic neurons that innervate sweat glands contain calcitonin gene-related peptide, vasoactive intestinal polypeptide, and acetylcholine. In addition, other chemicals besides the neuropeptides mentioned above are released from autonomic neurons along with the so-called classical neurotransmitters, norepinephrine and acetylcholine. For instance, some neurons synthesize a gas, nitric oxide, that functions as a neuronal messenger molecule. Thus, neural transmission in the autonomic nervous system involves the release of combinations of different neuroactive agents that affect both pre- and postsynaptic receptors.
Neurotransmitters released from nerve terminals bind to specific receptors, which are specialized macromolecules embedded in the cell membrane. The binding action initiates a series of specific biochemical reactions in the target cell that produce a physiological response. In the sympathetic nervous system, for example, there are five types of adrenergic receptors (receptors binding epinephrine): α1, α2, β1, β2, and β3. These adrenoceptors are found in different combinations in various cells throughout the body. Activation of α1- adrenoceptors in arterioles causes blood-vessel constriction, whereas stimulation of α2 autoreceptors (receptors located in sympathetic presynaptic nerve endings) functions to inhibit the release of norepinephrine. Other types of tissue have unique adrenoceptors. Heart rate and myocardial contractility, for example, are controlled by β1-adrenoceptors; bronchial smooth muscle relaxation is mediated by β2-adrenoceptors; and the breakdown of fat (lipolysis) is controlled by β3-adrenoceptors.
Cholinergic receptors (receptors binding acetylcholine) also are found in the sympathetic system (as well as the parasympathetic system). Nicotinic cholinergic receptors stimulate sympathetic postganglionic neurons, adrenal chromaffin cells, and parasympathetic postganglionic neurons to release their chemicals. Muscarinic receptors are associated mainly with parasympathetic functions and are located in peripheral tissues (e.g., glands and smooth muscle). Peptidergic receptors exist in target cells as well.
The length of time that each type of chemical acts on its target cell is variable. As a rule, peptides cause slowly developing, long-lasting effects (one or more minutes), whereas the classical transmitters produce short-term effects (about 25 milliseconds).
PARASYMPATHETIC NERVOUS SYSTEM
At a first approximation, chemical transmission in the sympathetic system appears simple: preganglionic neurons use acetylcholine as a neurotransmitter, whereas most postganglionic neurons utilize norepinephrine (noradrenaline)—with the major exception that postganglionic neurons innervating sweat glands use acetylcholine. On closer inspection, however, neurotransmission is seen to be more complex, because multiple chemicals are released, and each functions as a specific chemical code affecting different receptors on the target cell. In addition, these chemical codes are self-regulatory, in that they act on presynaptic receptors located on their own axon terminals.
The chemical codes are specific to certain tissues. For example, most sympathetic neurons that innervate blood vessels secrete both norepinephrine and neuropeptide Y; sympathetic neurons that innervate the submucosal neural plexus of the gut contain both norepinephrine and somatostatin; and sympathetic neurons that innervate sweat glands contain calcitonin gene-related peptide, vasoactive intestinal polypeptide, and acetylcholine. In addition, other chemicals besides the neuropeptides mentioned above are released from autonomic neurons along with the so-called classical neurotransmitters, norepinephrine and acetylcholine. For instance, some neurons synthesize a gas, nitric oxide, that functions as a neuronal messenger molecule. Thus, neural transmission in the autonomic nervous system involves the release of combinations of different neuroactive agents that affect both pre- and postsynaptic receptors.
Neurotransmitters released from nerve terminals bind to specific receptors, which are specialized macromolecules embedded in the cell membrane. The binding action initiates a series of specific biochemical reactions in the target cell that produce a physiological response. In the sympathetic nervous system, for example, there are five types of adrenergic receptors (receptors binding epinephrine): α1, α2, β1, β2, and β3. These adrenoceptors are found in different combinations in various cells throughout the body. Activation of α1- adrenoceptors in arterioles causes blood-vessel constriction, whereas stimulation of α2 autoreceptors (receptors located in sympathetic presynaptic nerve endings) functions to inhibit the release of norepinephrine. Other types of tissue have unique adrenoceptors. Heart rate and myocardial contractility, for example, are controlled by β1-adrenoceptors; bronchial smooth muscle relaxation is mediated by β2-adrenoceptors; and the breakdown of fat (lipolysis) is controlled by β3-adrenoceptors.
Cholinergic receptors (receptors binding acetylcholine) also are found in the sympathetic system (as well as the parasympathetic system). Nicotinic cholinergic receptors stimulate sympathetic postganglionic neurons, adrenal chromaffin cells, and parasympathetic postganglionic neurons to release their chemicals. Muscarinic receptors are associated mainly with parasympathetic functions and are located in peripheral tissues (e.g., glands and smooth muscle). Peptidergic receptors exist in target cells as well.
The length of time that each type of chemical acts on its target cell is variable. As a rule, peptides cause slowly developing, long-lasting effects (one or more minutes), whereas the classical transmitters produce short-term effects (about 25 milliseconds).
PARASYMPATHETIC NERVOUS SYSTEM
The parasympathetic nervous system primarily modulates visceral organs such as glands. Responses are never activated en masse as in the fight-or-flight sympathetic response. While providing important control of many tissues, the parasympathetic system, unlike the sympathetic system, is not crucial for the maintenance of life.
The parasympathetic nervous system is organized in a manner similar to the sympathetic nervous system. Its motor component consists of preganglionic and postganglionic neurons. The preganglionic neurons are located in specific cell groups (also called nuclei) in the brainstem or in the lateral horns of the spinal cord at sacral levels (segments S2–S4). (Because parasympathetic fibres exit from these two sites, the system is sometimes referred to as the craniosacral outflow.) Preganglionic axons emerging from the brainstem project to parasympathetic ganglia that are located in the head (ciliary, pterygopalatine [also called sphenopalatine], and otic ganglia) or near the heart (cardiac ganglia), embedded in the end organ itself (e.g., the trachea, bronchi, and gastrointestinal tract), or situated a short distance from the urinary bladder (pelvic ganglion). Both pre- and postganglionic neurons secrete acetylcholine as a neurotransmitter, but, like sympathetic ganglion cells, they also contain other neuroactive chemical agents that function as cotransmitters.
The third cranial nerve (oculomotor nerve) contains parasympathetic nerve fibres that regulate the iris and lens of the eye. From their origin in the Edinger-Westphal nucleus of the midbrain, preganglionic axons travel to the orbit and synapse on the ciliary ganglion. The ciliary ganglion contains two types of postganglionic neurons: one innervates smooth muscle of the iris and is responsible for pupillary constriction, and the other innervates ciliary muscle and controls the curvature of the lens.
Various secretory glands located in the head are under parasympathetic control. These include the lacrimal gland, which supplies tears to the cornea of the eye; salivary glands (sublingual, submandibular, and parotid glands), which produce saliva; and nasal mucous glands, which secrete mucus throughout the nasal air passages. The parasympathetic preganglionic neurons that regulate these functions originate in the reticular formation of the medulla oblongata. One group of parasympathetic preganglionic neurons belongs to the superior salivatory nucleus and lies in the rostral part of the medullary reticular formation. These neurons send axons out of the medulla in a separate branch of the seventh cranial nerve (facial nerve) called the intermediate nerve. Some of the axons innervate the pterygopalatine ganglion, and others project to the submandibular ganglion. Pterygopalatine ganglion cells innervate the vasculature of the brain and eye as well as the lacrimal gland, nasal glands, and palatine glands, while neurons of the submandibular ganglion innervate the submandibular and sublingual salivary glands. A second group of parasympathetic preganglionic neurons belongs to the inferior salivatory nucleus, located in the caudal part of the medullary reticular formation. Neurons of this group send axons out of the medulla in the ninth cranial (glossopharyngeal) nerve and to the otic ganglion. From this site, postganglionic fibres travel to and innervate the parotid salivary gland.
Preganglionic parasympathetic fibres of the 10th cranial (vagus) nerve arise from two different sites in the medulla oblongata. Neurons that slow heart rate arise from a part of the ventral medulla called the nucleus ambiguus, while those that control functions of the gastrointestinal tract arise from the dorsal vagal nucleus. After exiting the medulla in the vagus nerve and traveling to their respective organs, the fibres synapse on ganglion cells embedded in the organs themselves. The vagus nerve also contains visceral afferent fibres that carry sensory information from organs of the neck (larynx, pharynx, and trachea), chest (heart and lungs), and gastrointestinal tract into a visceral sensory nucleus located in the medulla called the solitary tract nucleus.
Enteric nervous system
The enteric nervous system is composed of two plexuses, or networks of neurons, embedded in the wall of the gastrointestinal tract. The outermost plexus, located between the inner circular and outer longitudinal smooth-muscle layers of the gut, is called the Auerbach, or myenteric, plexus. Neurons of this plexus regulate peristaltic waves that move digestive products from the oral to the anal opening. In addition, myenteric neurons control local muscular contractions that are responsible for stationary mixing and churning. The innermost group of neurons is called the Meissner, or submucosal, plexus. This plexus regulates the configuration of the luminal surface, controls glandular secretions, alters electrolyte and water transport, and regulates local blood flow.
Three functional classes of intrinsic enteric neurons are recognized: sensory neurons, interneurons, and motor neurons. Sensory neurons, activated by either mechanical or chemical stimulation of the innermost surface of the gut, transmit information to interneurons located within the Auerbach and the Meissner plexi, and the interneurons relay the information to motor neurons. Motor neurons in turn modulate the activity of a variety of target cells, including mucous glands, smooth muscle cells, endocrine cells, epithelial cells, and blood vessels.
Three functional classes of intrinsic enteric neurons are recognized: sensory neurons, interneurons, and motor neurons. Sensory neurons, activated by either mechanical or chemical stimulation of the innermost surface of the gut, transmit information to interneurons located within the Auerbach and the Meissner plexi, and the interneurons relay the information to motor neurons. Motor neurons in turn modulate the activity of a variety of target cells, including mucous glands, smooth muscle cells, endocrine cells, epithelial cells, and blood vessels.
Extrinsic neural pathways also are involved in the control of gastrointestinal functions. Three types exist: intestinofugal, sensory, and motor. Intestinofugal neurons reside in the gut wall; their axons travel to the preaortic sympathetic ganglia and control reflex arcs that involve large portions of the gastrointestinal tract. Sensory neurons relay information regarding distention and acidity to the central nervous system. There are two types of sensory neurons: sympathetic neurons, which originate from dorsal-root ganglia found at the thoracic and lumbar levels; and parasympathetic neurons, which originate in the nodose ganglion of the vagus nerve or in dorsal-root ganglia at sacral levels S2–S4. The former innervate the gastrointestinal tract from the pharynx to the left colic flexure, and the latter innervate the distal colon and rectum. Each portion of the gastrointestinal tract receives a dual sensory innervation: pain sensations travel via sympathetic afferent fibres, and sensations that signal information regarding the chemical environment of the gut travel by way of parasympathetic fibres and are not consciously perceived.
The third extrinsic pathway, exercising motor control over the gut, arises from parasympathetic preganglionic neurons found in the dorsal vagal nucleus of the medulla oblongata and from sympathetic preganglionic neurons in the lateral horns of the spinal cord. These pathways provide modulatory commands to the intrinsic enteric motor system and are nonessential in that basic functions can be maintained in their absence.
Through the pathways described above, the parasympathetic system activates digestive processes while the sympathetic system inhibits them. The sympathetic system inhibits digestive processes by two mechanisms: (1) contraction of circular smooth muscle sphincters located in the distal portion of the stomach (pyloric sphincter), small intestine (ileo-cecal sphincter), and rectum (internal anal sphincter), which act as valves to prevent the oral-to-anal passage (as well as reverse passage) of digestive products; and (2) inhibition of motor neurons throughout the length of the gut. In contrast, the parasympathetic system provides messages only to myenteric motor neurons.