The Peripheral Autonomic Nervous System Differs from the Somatic Motor System in a Number of Important Ways

The ANS differs from the somatic motor system in its target organs, in the number of neurons in its peripheral circuit, and in the nature of the synapse at the target organ. The somatic motor system innervates skeletal muscle, which is the muscle responsible for all movements of the body, as described in Chapters 5 and 6. In contrast, the ANS innervates smooth muscle, cardiac muscle, and glandular tissue (Figure 13-1). Cardiac muscle is the muscle of the heart (see Chapter 19). Smooth muscle is the muscle in blood vessels, in most of the gastrointestinal tract, in the bladder, and in other hollow visceral structures. Gland cells can also be part of visceral organs, as well as comprising nonvisceral glands (e.g., salivary glands, lacrimal gland).

The ANS also differs in the number of neurons it has in the peripheral nervous system (see Figure 13-1). The somatic nervous system has one neuron whose cell body is located in the central nervous system (CNS) and whose axon extends, uninterrupted, to the skeletal muscle, where the peripheral chemical synapse occurs. In contrast, the ANS has two peripheral neurons. The first, called a preganglionic neuron, also has its cell body in the CNS, but its axon innervates a second neuron in the chain, called the postganglionic neuron. The latter’s cell body is in a peripheral structure called a ganglion, a collection of neuronal cell bodies outside the CNS. There are chemically mediated synapses both between the preganglionic and postganglionic neurons and between the postganglionic neuron and the cells of its target organ.

The ANS also differs from the somatic motor system in the amount of myelin along the peripheral axons; the autonomic postganglionic neurons usually have slowly conducting, unmyelinated axons. In addition, somatic motor neurons always excite their skeletal muscle targets, whereas the autonomic postganglionic neurons can either excite or inhibit their targets. Furthermore, unlike the narrow synaptic cleft at the focal neuromuscular junction of a skeletal muscle cell, ANS target cells are often activated at a greater distance, by a highly branched postganglionic neuron with synaptic boutons (called varicosities; see Figure 27-7) distributed all along the length of these branches. This can contribute to a longer latency for, and greater spatial distribution of, postsynaptic cell activation by autonomic postganglionic neurons.

The Peripheral Autonomic Nervous System Has Two Subdivisions That Originate in the Central Nervous System and One That Does Not

The peripheral ANS is divided into two major subdivisions based on the respective CNS origin of their preganglionic neurons and on their synaptic transmitters at the target organ. These two subdivisions are the sympathetic nervous system and the parasympathetic nervous system. The enteric nervous system can be considered a third subdivision of the peripheral ANS. It is an extensive network of interconnected sensory, motor and interneurons within the gut (gastrointestinal tract) wall that can control gut function independently of the CNS. However, these neurons can also be influenced by the CNS through input from the sympathetic and parasympathetic subdivisions. The enteric nervous system will be discussed in more detail in reference to the regulation of gastrointestinal function in Chapter 27.

The Sympathetic Nervous System Originates from the Thoracolumbar Spinal Cord

The sympathetic nervous system generally has short preganglionic and long postganglionic axons. Preganglionic axons of the sympathetic nervous system leave the spinal cord by way of the ventral roots of the first thoracic through the third or fourth lumbar spinal nerves (Figure 13-2). For this reason, the sympathetic nervous system is often called the thoracolumbar system. The preganglionic axons pass through the ventral root and then a communicating branch (white ramus) to enter the paravertebral sympathetic ganglion chain (also called the sympathetic trunk), where most synapse with a postganglionic neuron (Figure 13-3, A). The ganglion chain actually extends from cervical to sacral regions and some of the thoracolumbar preganglionic neurons extend their axons rostrally or caudally within the chain to reach these cervical and sacral ganglia (see Figure 13-3, A, asterisk). A large complement of postganglionic axons from each of the chain ganglia enter nearby spinal nerves, through a different communicating ramus (gray ramus), and travel to the body wall or extremities to control blood vessels, sweat glands, or hair erector muscles (see Figure 13-3, A, #1). Another complement of these postganglionic neurons, mainly from thoracic or cervical chain ganglia, does not enter spinal nerves but forms separate nerves that travel respectively to thoracic viscera (e.g., heart, bronchi) or to organs and glands of the head (e.g., eye, lacrimal gland; see Figure 13-3, A, #2).

Some of the thoracolumbar preganglionic axons simply pass through the sympathetic chain ganglia without synapsing there. These axons form splanchnic nerves that synapse with postganglionic neurons in prevertebral ganglia (see Figure 13-3, A, #3), usually named for neighboring blood vessels (e.g., celiac, mesenteric). Postganglionic neurons of the prevertebral ganglia innervate abdominal and pelvic visceral organs. Some of the aforementioned splanchnic nerve fibers bypass the prevertebral ganglia and continue all the way to the adrenal medulla, where they synapse with rudimentary postganglionic neurons that make up the adrenal medullary secretory cells (see Figure 13-3, A, #4). These vestigial postganglionic neurons secrete their transmitter substance directly into the circulating blood. The transmitter substance, acting as a true hormone, is carried by the blood to all tissues of the body.

The Parasympathetic Nervous System Arises from the Brainstem and Sacral Spinal Cord

The parasympathetic nervous system generally has long preganglionic and short postganglionic axons. Preganglionic axons of the parasympathetic system leave the CNS by way of cranial nerves III (oculomotor), VII (facial), IX (glossopharyngeal), and X (vagus) and through several sacral spinal nerves. For this reason, it is called the craniosacral system (see Figure 13-2). The parasympathetic preganglionic axons leaving through cranial nerves III, VII, and IX synapse in well defined ganglia outside the skull (e.g., otic, submandibular; see Figure 13-3, B, top). The parasympathetic postganglionic neurons project to smooth muscle and glandular targets in the head (e.g., ciliary muscle, parotid gland).

Preganglionic axons leaving through cranial nerve X travel all the way to the body cavity to synapse in more diffuse parasympathetic ganglia located close to, or within, thoracic and abdominal viscera (see Figure 13-3, B, bottom). The short postganglionic neurons control the smooth muscle, cardiac muscle, and glandular cells of these organs.

Parasympathetic preganglionic axons leaving through sacral spinal nerves depart to form pelvic nerves that synapse in diffuse parasympathetic ganglia residing close to, or within, pelvic viscera (e.g. rectum, bladder; see Figure 13-3, C). The short postganglionic neurons control these organs, as well as erectile tissue of the genitals.

Most viscera receive both sympathetic and parasympathetic innervation (see Figure 13-2). Although the parasympathetic system originates in brainstem and sacral regions, it can provide parasympathetic innervation to organs in the thoracic and lumbar parts of the body, as just noted, by way of the vagus nerve (cranial nerve X). The sympathetic thoracolumbar system can influence organs in cranial and sacral regions by way of preganglionic sympathetic axons that travel to sympathetic postganglionic neurons in cervical and sacral regions of the sympathetic ganglion chain (see Figure 13-3, A, asterisk). Although blood vessels in all parts of the body receive sympathetic innervation, which most commonly produces vasoconstriction, most do not receive parasympathetic innervation (except those in glands and the external genitals).

Most Sympathetic and Parasympathetic Neurons Secrete Either Acetylcholine or Norepinephrine as a Neurotransmitter

As described in Chapter 5, acetylcholine is the neurotransmitter at the somatic neuromuscular synapse. Acetylcholine is also released by the preganglionic neurons at all autonomic ganglia (Figure 13-4). Parasympathetic postganglionic neurons release acetylcholine as well, onto their target organs. Acetylcholine-releasing synapses are often called cholinergic. Most anatomically sympathetic postganglionic neurons secrete norepinephrine onto their targets. Norepinephrine-releasing synapses are often called adrenergic. However, in several species, anatomically sympathetic postganglionic neurons traveling to sweat glands secrete acetylcholine, as do some of the sympathetic postganglionic neurons to blood vessels in skeletal muscle, where they can produce vasodilation.

In the case of the adrenal medulla, incoming preganglionic axons release acetylcholine, but the neuroendocrine-like, postganglionic chromaffin cells release primarily epinephrine and some norepinephrine into the circulating blood. These chromaffin cells can be considered structural and functional analogues of sympathetic postganglionic neurons.

It is important that, when released, the neurotransmitter not linger in the synaptic cleft. The neurotransmitter must be either destroyed in the cleft or dissipated so that the postsynaptic membrane can recover its resting potential and be ready for the next synaptic transmission. Because some synapses can transmit impulses up to several hundred times per second, neurotransmitter destruction must occur quickly. In the case of acetylcholine, acetylcholinesterase destroys the transmitter in the cleft. For norepinephrine, reuptake by the presynaptic neuron is the principal way in which its synaptic effect on the postsynaptic membrane is terminated. The hormonal actions of circulating epinephrine and norepinephrine released by the adrenal medulla, however, are primarily terminated by the enzyme catechol-O-methyltransferase (COMT), with a lesser contribution of the enzyme monoamine oxidase (MAO). These enzymes are widely distributed in the body, with highest concentrations in the liver and kidney.

Acetylcholine and Norepinephrine Have Different Postsynaptic Receptors

The neurotransmitters secreted by the ANS typically stimulate their target organ by first binding with a postsynaptic receptor. These receptors are proteins in the cell membrane. When the transmitter binds with the postsynaptic receptor, the membrane’s permeability to selected ions is often changed, and the postsynaptic membrane potential either increases or decreases, with a resulting change in the probability of action potentials in the postsynaptic cell.

Acetylcholine stimulates two different types of receptors (see Figure 13-4). Muscarinic acetylcholine receptors are G-protein–coupled receptors (GPCRs; see Chapter 1) found on all the target cells stimulated by postganglionic parasympathetic neurons and by cholinergic postganglionic neurons of the sympathetic nervous system. Faster acting nicotinic receptors are ligand-gated ion channels (see Chapter 1) found at all synapses between autonomic preganglionic and postganglionic neurons and at the somatic neuromuscular junction.

The classification of major types and subtypes of neurotransmitter receptors is usually based upon various combinations of the following: responses to agonist or antagonist drugs, distribution among various tissues and organs, signal transduction mechanism (e.g., G protein-coupled, ligand-gated). Muscarinic receptors were named because they are stimulated by muscarine, a toadstool poison. Muscarine does not stimulate nicotinic receptors. Nicotine stimulates the nicotinic receptors but not muscarinic receptors. Acetylcholine stimulates both, and different drugs block each receptor. For example, atropine blocks muscarinic receptors, whereas curare blocks nicotinic receptors. Although there are respective subtypes of nicotinic (e.g., N_m, N_n) and muscarinic (e.g., M₁-M₅) acetylcholine receptors, there are few therapeutic drugs that can distinguish among subtype members.

Adrenergic receptors are located at synapses between peripheral target tissues and sympathetic postganglionic neurons that release norepinephrine. However, these receptors can also be stimulated by the release of epinephrine and norepinephrine into the bloodstream from the adrenal medulla. There are two major types of adrenergic receptors, called alpha (α) and beta (β) receptors. The β receptors have been further subdivided into β₁ and β₂ receptors, on the basis of the effect of adrenergic blocking and stimulating drugs. There is now evidence for a third class of β receptor (β₃, found in fat cells), and for two classes of α receptors (α₁ and α₂) that can each be divided into additional subtypes. All adrenergic receptors are GPCRs, and the various subtypes, like the cholinergic receptor subtypes, have differential distributions among various tissues. There are many clinically useful drugs that can distinguish among the members within adrenergic receptor subtype groups.

Neurotransmitters Other Than Acetylcholine and Norepinephrine Play Some Role in Peripheral Autonomic Function

As more of a rule than an exception, individual neurons are capable of releasing more than one neurotransmitter. Multiple release often depends upon how vigorously the neurons are activated by presynaptic stimulation. Therefore, preganglionic and postganglionic sympathetic and parasympathetic neurons that release either acetylcholine or norepinephrine are respectively capable of releasing co-transmitters under certain circumstances. Most often these co-transmitters are peptides (e.g., vasoactive intestinal peptide, neuropeptide Y, luteinizing hormone-releasing hormone), but some purine (e.g., ATP) and atypical neurotransmitter (e.g., nitric oxide) co-release has been demonstrated as well. Often the postsynaptic response to release of a neurotransmitter is modified by the release of a co-transmitter from the same neuron. For example, acetylcholine released from parasympathetic postganglionic neurons can activate salivary glands, but co-release of vasoactive intestinal peptide from the same neurons can affect blood vessel diameter in the target region as well.

Acetylcholine and norepinephrine can also be found in the enteric nervous system: acetylcholine is released by excitatory enteric neurons of the gut (see Chapter 27), and postganglionic sympathetic neurons can release norepinephrine into enteric neuronal plexuses to induce inhibition. Like the sympathetic/parasympathetic systems, various enteric neurons also employ vasoactive intestinal peptide, neuropeptide Y, ATP, and nitric oxide. However, the variety of neurotransmitters other than acetylcholine and norepinephrine, employed by neurons of the enteric nervous system, is much more extensive than that found among the sympathetic and parasympathetic systems.