The Autonomic Nervous System

As a convenience in understanding the nervous system, we subdivide it into anatomic and functional groups that we refer to as systems. Examples of these are autonomic, limbic, reticular formation, visual, pyramidal, and extrapyramidal. The anatomic components of the autonomic nervous system (ANS) are controversial. Some consider that the ANS only consists of the general visceral efferent (GVE), lower motor neuron (LMN), and its parasympathetic and sympathetic components. Others, including ourselves, prefer a more expansive definition that correlates its function with its anatomy and consider that the ANS has a plethora of components in the central nervous system (CNS) as well as in the peripheral nervous system (PNS). Its primary afferents are the general visceral afferent (GVA) system and its efferent LMN is the GVE system with its parasympathetic and sympathetic components.

In this text the ANS is considered to be an anatomic and physiologic system with central and peripheral components. It includes higher centers in the hypothalamus, midbrain, pons, and medulla as well as tracts and nuclei in the spinal cord. The hypothalamus is the primary integrating center of the ANS. Nuclei in its rostral portion subserve the parasympathetic division of the GVE-LMN. Nuclei in its caudal portion subserve the sympathetic division of the GVE-LMN. These hypothalamic nuclei receive afferents from the cerebrum by way of numerous pathways, from thalamic nuclei and from GVA projection pathways. The hypothalamus influences the activity of the metabolic centers in the reticular formation of the midbrain, pons, and medulla. These centers control the activity of visceral smooth muscle, glands, and cardiac muscle by means of the GVE-LMN, which is located in specific cranial nerves and all spinal nerves.

The ANS is concerned with activating emergency mechanisms and with the repair and preservation of the internal environment of the body. It maintains a steady state in the internal environment for the continuous efficient function of the body, which is called homeostasis. In order to carry out these functions, the ANS must receive information from the body via sensory neurons in the GVA system, then process this information in centers in the brain and send responses back to the body by brainstem and spinal cord pathways that activate LMNs in the GVE system.

Despite efforts to simplify the anatomy of this system and especially its GVE component, the complexity of it continues to defy simple organizational principles. Exceptions to the rules that we have set are continually disclosed, and this chapter makes no attempt to document all of these.

General Visceral Efferent System

The GVE system is grouped anatomically and physiologically into two components: the parasympathetic and sympathetic systems. This LMN is a two-neuron system between the CNS and the effector organ innervated. These two neurons are historically referred to as the preganglionic and postganglionic neurons. Only the axon of the second neuron is postganglionic. Therefore, in this text, the second LMN in this system will be referred to as the ganglionic neuron. The cell body of the preganglionic neuron is in the gray matter of the CNS and the cell body of the ganglionic neuron is in an autonomic ganglion in the PNS. The telodendron of the preganglionic neuron synapses on the dendritic zone of the ganglionic neuron. The neurotransmitter released at the synapse between these two neurons in the autonomic ganglion is acetylcholine. The sympathetic system is referred to as the thoracolumbar system based on the location of the cell body of the first neuron, the preganglionic neuron, that is in the lateral gray horn from spinal cord segments T1 to approximately L4 or L5. As a general rule the sympathetic ganglia are located close to the CNS and the postganglionic axons are fairly long. With a few exceptions the neurotransmitter released at the telodendron of the sympathetic postganglionic axon is norepinephrine. Thus the sympathetic system is referred to as the adrenergic system. The parasympathetic system is referred to as the craniosacral system because the cell bodies of the preganglionic neurons are located in the brainstem nuclei of cranial nerves III, VII, IX, or X, or in the sacral spinal cord segments. As a general rule the ganglia of this parasympathetic system are located in or fairly close to the effector organ and the postganglionic axons are short. Acetylcholine is the neurotransmitter released at the telodendron of the postganglionic axon. Thus this parasympathetic system is called the cholinergic system.

Despite its name this ANS is not strictly autonomous as its functions are closely integrated with somatic activity. Most structures innervated by the GVE system receive both parasympathetic and sympathetic axons with functions that are not always antagonistic. The activity of the GVE system is integrated for neurologic regulation of normal body functions as well as its response to stress.

Parasympathetic Division

Parasympathetic preganglionic axons leave the brainstem as part of cranial nerves III, VII, IX, and X (Figs. 15-1 and 15-2). The axons in nerves III, VII, and IX are distributed to the head region, whereas the vagus nerve distributes autonomic axons to the cervical, thoracic, and abdominal viscera as far caudally as the left colic flexure. Parasympathetic preganglionic axons also leave the spinal cord as part of the ventral roots of the sacral nerves and become part of the pelvic plexus. It is this brainstem and sacral spinal cord origin of parasympathetic axons that is described by the term craniosacral as a synonym for parasympathetic. Other routes of distribution may exist. For example, a rich and widely distributed cholinergic innervation of cerebral blood vessels has been described in the dog (Amenta et al., 1980). The nerves are restricted mainly to the adventitia, are more prominent in arteries, remain intact after removal of the cranial cervical ganglia, and are therefore assumed to be parasympathetic.

Oculomotor (III)

Preganglionic neurons lie in the parasympathetic nucleus of the oculomotor nerve (nucleus parasympathici oculomotorii) which is unpaired in the dog and is located on the median plane just ventral to the central gray substance of the rostral mesencephalon (Figs. 15-1 and 15-2). This nucleus is called the nucleus of Edinger-Westphal in humans. The axons run as part of the third cranial nerve through the middle cranial fossa to leave the cranial cavity via the orbital fissure. They leave the oculomotor nerve by a short root and terminate at the ciliary ganglion (ganglion ciliare). Synapse occurs in the ciliary ganglion, and the postganglionic axons leave as the short ciliary nerves. They supply the ciliary muscle, which regulates lens curvature, and the sphincter of the iris, which, when activated, reduces pupillary diameter. Distribution of cholinergic as well as adrenergic innervation in the eye is described (Gwin et al., 1979). An accessory ciliary ganglion has been described in 13 mammalian species, including canines in which it is located approximately 4 mm from the ciliary ganglion on one of the short ciliary nerves (Kuchiiwa et al., 1989).

Facial (VII)

The cell bodies of the preganglionic parasympathetic neurons associated with the facial nerve form two small nuclei in the medulla, the parasympathetic nuclei of the facial and intermediate nerves (Figs. 15-1 and 15-2). The parasympathetic nucleus of the facial nerve (nucleus parasympatheticus n. facialis) is closely associated with the somatic motor facial nucleus (Azuma et al., 1983). The preganglionic axons of these small cell bodies emerge from the medulla in the pars intermedia of the facial nerve, the intermediate nerve (n. intermedius) which immediately follows the facial nerve. Within the facial canal of the petrosal portion of the temporal bone, these preganglionic axons leave the facial nerve in the major petrosal nerve (n. petrosus major) and continue into the orbit in the nerve of the pterygoid canal (n. canalis pterygoidei) (Wakata, 1975) to terminate in synapses in the pterygopalatine ganglion (ganglion pterygopalatinum) located medial to the sphenopalatine nerve on the surface of the medial pterygoid muscle. Postganglionic axonal distribution to the lacrimal gland is not well defined. Apparently, some axons may go directly as small branches, and some may run with the lacrimal and zygomatic nerves. Other postganglionic axons go to glands and smooth muscle of the nasal and oral cavities via branches of the fifth cranial nerve (Jung et al., 1926; Nitschke, 1976).

The parasympathetic nucleus of the intermediate nerve (nucleus parasympathticus n. intermedii) is located in the medulla dorsomedial to the somatic motor nucleus. These preganglionic axons leave the brainstem with the pars intermedia of the facial nerve. They join the main trunk of the facial nerve (Van Buskirk, 1945) and as they traverse the facial canal of the petrosal part of the temporal bone they leave as part of the chorda tympani nerve (Foley, 1945). The latter traverses the tympanic cavity and joins the lingual branch of the mandibular nerve. Synapse occurs in the mandibular ganglion (ganglion mandibulare) and the sublingual ganglion (ganglion sublinguale) and the postganglionic axons innervate the sublingual and mandibular salivary glands. The parasympathetic nucleus of the intermediate nerve also supplies glands of the tongue (see Chapter 7, The Tongue).

Glossopharyngeal (IX)

See Figs. 15-1 and 15-2. The cell bodies of the preganglionic neurons that initially travel with the glossopharyngeal nerve are located in the medulla in the parasympathetic nucleus of the glossopharyngeal nerve (nucleus parasympatheticus n. glossopharyngei). This nucleus is located at the rostral end of the parasympathetic nucleus of the vagus nerve lateral to the hypoglossal nucleus and adjacent to the floor of the fourth ventricle. The preganglionic axons leave the medulla in the rootlets of the glossopharyngeal nerve, which enters the jugular foramen. These preganglionic axons branch from the glossopharyngeal nerve and become part of the tympanic plexus (plexus tympanicus) on the ventral surface of the petrosal portion of the temporal bone within the tympanic cavity. They leave the plexus in the minor petrosal nerve (n. petrosal minor) to synapse in the otic ganglion (ganglion oticum), which is adjacent to the external opening of the oval foramen and the origin of the mandibular nerve from the trigeminal nerve. The postganglionic axons run with the auriculotemporal nerve, a branch of the mandibular nerve to their destination on the gland cells of the parotid salivary gland. A large number of these postganglionic axons also run in the adventitia of the maxillary artery and a small number of axons run in the facial nerve (Holmberg, 1971). The zygomatic salivary gland also receives parasympathetic postganglionic axons from the otic ganglion. The otic ganglion is a plexiform structure containing a number of small ganglia and having close contact with the maxillary artery (Gienc & Kuder, 1983).

Vagus (X)

(Figs. 15-1, 15-3, 15-4, and 15-6.)

FIGURE 15-3 Nerves of the pharyngeal region, lateral aspect. (The diagastric muscle and superficial structures have been removed.)

The vagus nerve contains a number of functional components that include a large component of GVA axons and a smaller component of preganglionic parasympathetic GVE axons. The cervical portion of the vagus nerve is said to contain more than 80% “C” axons, with the balance myelinated (Fussey et al., 1973). The majority of the “C” axons are assumed to be afferent and the rest efferent parasympathetic fibers originating in the parasympathetic nucleus of the vagus nerve (nucleus parasympatheticus vagi). The paired nucleus is located in the dorsal part of the caudal medulla oblongata lateral to the hypoglossal nucleus ventral to the floor of the fourth ventricle. Various branches of the vagus are discussed in this section, but distribution of the branches other than preganglionic parasympathetic GVE axons is described in the section on cranial nerves. The vagal rootlets leave the brain along the dorsolateral sulcus of the medulla oblongata in series with the rootlets of cranial nerves IX and XI. Close association of some of the vagal axons with those of the accessory (XI) nerve for a very short distance has led to the description of these vagal axons as part of the cranial root of the accessory nerve in some species.

A few millimeters distal to the origin of the vagus is located the small proximal vagal ganglion (ganglion proximale n. vagi). It is located at the level of the tympanooccipital fissure and contains unipolar general somatic afferent neurons whose axons are distributed with the auricular branch (r. auricularis) of the vagus. This branch leaves the vagus at approximately the level of the proximal vagal ganglion and has been shown to be distributed in part via branches of the seventh cranial nerve. There are also some branches in the tongue of the dog that have their cell bodies in the proximal ganglion of the vagus.

The pharyngeal branch (r. pharyngeus) of the vagus is given off between the proximal and distal vagal ganglia (ganglion distale n. vagi). The latter ganglion is primarily composed of unipolar GVA neurons that have their peripheral distribution in the viscera.

The cranial laryngeal nerve (n. laryngeus cranialis) leaves the vagus at the level of the distal ganglion. The sympathetic cranial cervical ganglion is located rostral and medial to the distal vagal ganglion. The epineurial sheaths of the two ganglia may be separate or may show variable degrees of fusion. By careful dissection, it is possible to peel the epineurial sheath away from the vagus and its ganglia, thereby clearly demonstrating the branches that leave the vagus. In some specimens a small, unnamed bundle of vagal axons may be seen to bypass the distal ganglion.

Distal to the distal vagal ganglion, the vagus joins the sympathetic trunk, and the two are bound in a common sheath along the entire cervical region. The sympathetic trunk may retain a rounded contour (in cross-section) or may assume a crescent shape where it is closely applied to the vagus. In some specimens it is nevertheless possible to easily separate the two by dissection.

At the level of the middle cervical ganglion (Fig. 15-5) the right recurrent laryngeal nerve (n. laryngeus recurrens) leaves the right vagus and passes dorsally around the caudal side of the right subclavian artery. As it runs cranially on the trachea, it lies deep to the common carotid artery in the angle between the longus colli muscle and the trachea. Near its origin, the right recurrent laryngeal nerve gives off a fairly large branch, the cervical cardiac nerve (n. cardiacus cervicalis), which receives contributions from the middle cervical ganglion, the vagal trunk, and the left recurrent laryngeal nerve. It is distributed mainly to plexuses along the right and left coronary arteries. The cervical cardiac nerve contains postganglionic sympathetic, preganglionic parasympathetic, and visceral afferent axons for the heart.

Terminal parasympathetic ganglia in the heart contain neuronal cell bodies that differ markedly in size (Nonidez, 1939). As a consequence, the postganglionic axons also vary in diameter. These axons lie in the walls of the atria and the interatrial septum and form extensive cardiac plexuses. Smaller branches leave the plexuses and end as ring-shaped, club-shaped, or reticulated enlargements, which contact the surface of the cardiac muscle fibers. Similar enlargements may also occur along the course of the finer branchings. Terminations are especially abundant among the specialized muscle fibers of the sinoatrial (SA) and atrioventricular (AV) node. These nodes are also richly supplied with adrenergic fibers (Dahlström et al., 1965). Postganglionic parasympathetic axons of the cardiac ganglia are also distributed via nerve plexuses along branches of the coronary arteries. These axons form plexuses in the adventitia and finally end in relation to the smooth muscle cells of the outer media. Primarily, these axons innervate the arteries of the atrium and proximal part of the ventricles. Most of the parasympathetic distribution is to structures dorsal to the coronary sulcus, whereas sympathetic axons innervate the ventricles. Further information on intrinsic innervation of the heart may be found in Tcheng (1950, 1951), Holmes (1956, 1957), Uchizono (1964), Hirsch et al. (1964, 1965), Napolitano et al. (1965), Ehinger et al. (1967), Kent et al. (1974), Kyösola et al. (1976), Denn and Stone (1976), Geis et al. (1973), Martin et al. (1970), Coleridge et al. (1973), and Hopkins and Armour (1984).

The right vagus nerve, having usually separated from the sympathetic trunk a short distance cranial to the level of the middle cervical ganglion, runs ventral to the right subclavian artery and continues caudally along the lateral surface of the trachea. At the level of the subclavian artery, the ansa subclavia may be intimately attached to the vagus for a short distance. Also in this region the vagus and recurrent laryngeal nerves may receive branches from the middle cervical ganglion or ansa subclavia. Distal to the origin of the recurrent laryngeal nerve, the vagus gives off two or more fine cardiac branches. The cranial branches go mainly to the pretracheal plexus. The caudal cardiac branches distribute to the dorsal wall of the right atrium.

The main trunk of the right vagus continues caudally dorsal to the root of the lung. At this level it gives off several prominent branches along the bronchi (Ziemianski et al., 1967). Parasympathetic ganglia are found in the lung, and postganglionic parasympathetic axons have been traced to smooth muscle and glandular structures. The lung is also richly innervated with a wide variety of receptor structures as far distally as the alveoli. Receptors have been described in smooth muscle, tracheal and bronchial epithelium, respiratory bronchioles, alveolar ducts, and alveolar walls (Elftmann, 1943). The vagus supplies branches directly to the trachea and esophagus and also via the recurrent laryngeal nerve.

Immediately caudal to the root of the lung, both right and left vagi split into dorsal and ventral branches. The ventral branch of the right fuses with its left counterpart to form the ventral vagal trunk (truncua vaglis ventralis). A similar anastomosis occurs between right and left dorsal vagal branches more distally near the diaphragm to form the dorsal vagal trunk (truncus vagalis dorsalis).

Both dorsal and ventral vagal trunks supply branches to the esophagus before passing through the diaphragm at the esophageal hiatus. On reaching the abdominal cavity, the ventral vagus becomes plexiform for a short distance. Branches from this plexus supply mainly the liver and stomach. The hepatic branches (usually two or three) originate from both vagal trunks and run in the lesser omentum to the liver (Chiu, 1943). These pass between the caudate and left lateral lobe of the liver to form a simple plexus just rostral to the porta hepatis. Autonomic nerve branches are distributed from the plexuses to the cystic duct, gallbladder, left lateral lobe of the liver, and bile duct. Groups of axons also pass along the right gastric and cranial pancreaticoduodenal arteries to the pancreas and along the right gastric artery to the pylorus. A small filament may go directly to the duodenum.

The second group of three or four gastric branches from the ventral vagus supply the parietal surface of the stomach. Some parasympathetic axons join the sympathetic plexus on the branches of the left gastric artery (Mizeres, 1955a).

The dorsal vagal trunk supplies the cardiac region of the stomach and then forms a plexus on its visceral surface. Distribution is mainly to the lesser curvature and pyloric regions of the stomach. Branches of the dorsal vagal trunk may also join the celiac, left gastric, hepatic, and cranial mesenteric nerve plexuses associated with the corresponding arteries. Further references on abdominal distribution of the vagus nerve are those of Obrebowski (1965), Kapeller (1965), Mizeres (1955a), and Kemp (1973).

Information on vagal parasympathetic distribution caudal to the stomach is sparse, but there seems to be general agreement that these fibers reach as far caudally as the left colic flexure.

Branching and distribution of the left vagus are similar to the right as far distally as the level of the middle cervical ganglion. Here a branch leaves the vagus to join a branch from the middle cervical ganglion, resulting in formation of a cervical cardiac nerve. This is distributed to the base of the brachiocephalic trunk and ventral surface of the aortic arch.

It must be emphasized that details of autonomic nerve distribution to the heart are extremely variable, particularly with respect to origin of axons. Many of the nerves to the heart are mixed in the sense that they carry sympathetic, parasympathetic, and visceral afferent fibers. Terminology is varied and often confusing. In general it can be said that impulses propagated in sympathetic axons tend to accelerate heart rate and force of contraction, whereas parasympathetic stimulation reduces heart rate. Branches leave the left recurrent laryngeal nerve near its origin and go to the left atrium or plexuses that supply it. Other branches to the left atrium leave the vagus distal to the origin of the recurrent nerve. The vagus also contributes axons to certain other cardiac nerves, which is discussed with the sympathetic system.

Axons that make up the left recurrent laryngeal nerve leave the vagus at the level of the aortic arch and loop around the arch caudal to the ligamentum arteriosum. The recurrent laryngeal nerve then proceeds cranially along the left ventrolateral surface of the trachea adjacent to the ventromedial side of the esophagus. Branches are supplied to the trachea and esophagus as the nerve passes to its termination in the larynx (Hwang et al., 1948; Watson, 1974). In the cervical region the left recurrent laryngeal supplies more branches to the esophagus than it does to the trachea. The opposite is true of the right recurrent laryngeal nerve. In dogs whose esophagus lies to the right of the midline in the cervical region, there is a more even distribution of branches of right and left recurrent laryngeal nerves to both trachea and esophagus.

Cranial to the root of the lung, the left vagus may contribute a variable number of axons to the cardiac nerves, as previously noted. Several branches leave the left vagus for distribution along the bronchi much as occurs on the right side. Distal to the root of the lung, the left vagus divides into dorsal and ventral branches, each of which joins its counterpart of the right side to result in dorsal and ventral vagal trunks. Their distribution has been discussed.

Parasympathetic ganglionic neurons may be found scattered in the walls of structures that they supply or else as part of well-defined plexuses in similar regions. These intramural nerve plexuses are most prominent in the digestive tract (Filogamo, 1950; Lawrentjew, 1931; Richardson, 1960; Schofield, 1961). The myenteric plexus (plexus myentericus), is located between the longitudinal and circular muscle layers, and the submucosal plexus (plexus submucosus) lies in the submucosa of the digestive tube (El’bert, 1956; Leaming & Cauna, 1961). Ganglia are common in these enteric plexuses (plexus entericus). Prominent ganglionated plexuses are also found in the atria of the heart. Much of their regulating effect is thought to be mediated by way of the SA and AV nodes.