The Autonomic Division

The autonomic division of the efferent nervous system (or autonomic nervous system for short) is also known in older writings as the vegetative nervous system, reflecting the observation that its functions are not under voluntary control. The word autonomic comes from the same roots as autonomous, meaning self-governing. Another name for the autonomic division is visceral nervous system because of its control over internal organs.

The autonomic division is subdivided into sympathetic and parasympathetic branches (often called the sympathetic and parasympathetic nervous systems). Some parts of the sympathetic branch were first described by the Greek physician Claudius Galen (ca. 130–200 c.e.), who is famous for his compilation of anatomy, physiology, and medicine as they were known during his time. As a result of his dissections, Galen proposed that “animal spirits” flowed from the brain to the tissues through hollow nerves, creating “sympathy” between the different parts of the body. Galen’s “sympathy” later gave rise to the name for the sympathetic branch. The prefix para-, for the parasympathetic branch, means beside or alongside.

The sympathetic and parasympathetic branches can be distinguished anatomically, but there is no simple way to separate the actions of the two branches on their targets. They are distinguished best by the type of situation in which they are most active. The picnic scene that began the chapter illustrates the two extremes at which the sympathetic and parasympathetic branches function. If you are resting quietly after a meal, the parasympathetic branch is dominant, taking command of the routine, quiet activities of day-to-day living, such as digestion. Consequently, parasympathetic neurons are sometimes said to control “rest and digest” functions.

In contrast, the sympathetic branch dominates in stressful situations, such as the potential threat from the snake. One of the most dramatic examples of sympathetic action is the fight-or-flight response, in which the brain triggers massive simultaneous sympathetic discharge throughout the body. As the body prepares to fight or flee, the heart speeds up; blood vessels to muscles of the arms, legs, and heart dilate; and the liver starts to produce glucose to provide energy for muscle contraction. Digestion becomes a low priority when life and limb are threatened, and so blood is diverted from the gastrointestinal tract to skeletal muscles.

The massive sympathetic discharge that occurs in fight-or-flight situations is mediated through the hypothalamus and is a total-body response to a crisis. If you have ever been scared by the squealing of brakes or a sudden sound in the dark, you know how rapidly the nervous system can influence multiple body systems. Most sympathetic responses are not the all-out response of a fight-or-flight reflex, however, and more importantly, activating one sympathetic pathway does not automatically activate them all.

The role of the sympathetic nervous system in mundane daily activities is as important as a fight-or-flight response. For example, one key function of the sympathetic branch is control of blood flow to the tissues. Most of the time, autonomic control of body function “seesaws” back and forth between the sympathetic and parasympathetic branches as they cooperate to fine-tune various processes (Fig. 11.1). Only occasionally, as in the fight-or-flight example, does the seesaw move to one extreme or the other.

FIG. 11.1 The autonomic division

Concept Check

  1. The afferent division of the nervous system has what two components?

  2. The central nervous system consists of the           and the            .

Autonomic Reflexes Are Important for Homeostasis

The autonomic nervous system works closely with the endocrine system and the behavioral state system [here] to maintain homeostasis in the body. Sensory information from somatosensory and visceral receptors goes to homeostatic control centers in the hypothalamus, pons, and medulla (Fig. 11.2). These centers monitor and regulate important functions such as blood pressure, temperature control, and water balance (Fig. 11.3).

FIG. 11.2 Integration of autonomic function

FIG. 11.3 Autonomic control centers

The hypothalamus also contains neurons that act as sensors, such as osmoreceptors, which monitor osmolarity, and thermoreceptors, which monitor body temperature. Motor output from the hypothalamus and brain stem creates autonomic responses, endocrine responses, and behavioral responses such as drinking, food-seeking, and temperature regulation (getting out of the heat, putting on a sweater). These behavioral responses are integrated in brain centers responsible for motivated behaviors and control of movement.

In addition, sensory information integrated in the cerebral cortex and limbic system can create emotions that influence autonomic output, as Figure 11.2 illustrates. Blushing, fainting at the sight of a hypodermic needle, and “butterflies in the stomach” are all examples of emotional influences on autonomic functions. Understanding the autonomic and hormonal control of organ systems is the key to understanding the maintenance of homeostasis in virtually every system of the body.

Some autonomic reflexes are capable of taking place without input from the brain. These spinal reflexes [Fig. 9.7 ] include urination, defecation, and penile erection—body functions that can be influenced by descending pathways from the brain but do not require this input. For example, people with spinal cord injuries that disrupt communication between the brain and spinal cord may retain some spinal reflexes but lose the ability to sense or control them.

Antagonistic Control Is a Hallmark of the Autonomic Division

The sympathetic and parasympathetic branches of the autonomic nervous system display all four of Walter Cannon’s properties of homeostasis: (1) preservation of the fitness of the internal environment, (2) up-down regulation by tonic control, (3) antagonistic control, and (4) chemical signals with different effects in different tissues [here].

Many internal organs are under antagonistic control, in which one autonomic branch is excitatory and the other branch is inhibitory (see the table on the right side of Fig. 11.5). For example, sympathetic innervation increases heart rate, while parasympathetic stimulation decreases it. Consequently, heart rate can be regulated by altering the relative proportions of sympathetic and parasympathetic control.

Exceptions to dual antagonistic innervation include the sweat glands and the smooth muscle in most blood vessels. These tissues are innervated only by the sympathetic branch and rely strictly on tonic (up-down) control.

The two autonomic branches are usually antagonistic in their control of a given target tissue, but they sometimes work cooperatively on different tissues to achieve a common goal. For example, blood flow for penile erection is under control of the parasympathetic branch, while muscle contraction for sperm ejaculation is directed by the sympathetic branch.

In some autonomic pathways, the neurotransmitter receptor determines the response of the target tissue. For instance, most blood vessels contain one type of adrenergic receptor [here] that causes smooth muscle contraction (vasoconstriction). However, some blood vessels also contain a second type of adrenergic receptor that causes smooth muscle relaxation (vasodilation). Both receptors are activated by the catecholamines norepinephrine and epinephrine [here]. In these blood vessels, the adrenergic receptor, not the chemical signal, determines the response [here].

Concept Check

  1. Define homeostasis.

Autonomic Pathways Have Two Efferent Neurons in Series

All autonomic pathways (sympathetic and parasympathetic) consist of two neurons in a series (Fig. 11.4). The first neuron, called the preganglionic neuron, originates in the central nervous system (CNS) and projects to an autonomic ganglion outside the CNS. There, the preganglionic neuron synapses with the second neuron in the pathway, the postganglionic neuron. This neuron has its cell body in the ganglion and projects its axon to the target tissue. (A ganglion is a cluster of nerve cell bodies that lie outside the CNS. The equivalent in the CNS is a nucleus [p. here].)

FIG. 11.4 Autonomic pathways

Divergence [here] is an important feature of autonomic pathways. On average, one preganglionic neuron entering a ganglion synapses with 8 or 9 postganglionic neurons. Some synapse on as many as 32 neurons! Each postganglionic neuron may then innervate a different target, meaning that a single signal from the CNS can affect a large number of target cells simultaneously.

In the traditional view of the autonomic division, autonomic ganglia were simply a way station for the transfer of signals from preganglionic neurons to postganglionic neurons. We now know, however, that ganglia are more than a simple collection of axon terminals and nerve cell bodies: they also contain neurons that lie completely within them. These neurons enable the autonomic ganglia to act as mini-integrating centers, receiving sensory input from the periphery of the body and modulating outgoing autonomic signals to target tissues. Presumably, this arrangement means that a reflex could be integrated totally within a ganglion, with no involvement of the CNS. That pattern of control is known to exist in the enteric nervous system [here], which is discussed with the digestive system [Chapter  21].

Sympathetic and Parasympathetic Branches Originate in Different Regions

How, then, do the two autonomic branches differ anatomically? The main anatomical differences are (1) the pathways’ point of origin in the CNS and (2) the location of the autonomic ganglia. As Figure 11.5 shows, most sympathetic pathways (red) originate in the thoracic and lumbar regions of the spinal cord. Sympathetic ganglia are found primarily in two ganglion chains that run along either side of the bony vertebral column, with additional ganglia along the descending aorta. Long nerves (axons of postganglionic neurons) project from the ganglia to the target tissues. Because most sympathetic ganglia lie close to the spinal cord, sympathetic pathways generally have short preganglionic neurons and long postganglionic neurons.

FIG. 11.5 Sympathetic and parasympathetic divisions

Figure Question

  1. What is an advantage of having ganglia in the sympathetic chain linked to each other?

  2. Which organs have antagonistic control by sympathetic and parasympathetic divisions? Which have cooperative control, with sympathetic and parasympathetic division each contributing to a function?

Many parasympathetic pathways (shown in blue in Fig. 11.5) originate in the brain stem, and their axons leave the brain in several cranial nerves [here]. Other parasympathetic pathways originate in the sacral region (near the lower end of the spinal cord) and control pelvic organs. In general, parasympathetic ganglia are located either on or near their target organs. Consequently, parasympathetic preganglionic neurons have long axons, and parasympathetic postganglionic neurons have short axons.

Parasympathetic innervation goes primarily to the head, neck, and internal organs. The major parasympathetic tract is the vagus nerve (cranial nerve X), which contains about 75% of all parasympathetic fibers. This nerve carries both sensory information from internal organs to the brain and parasympathetic output from the brain to organs.

Vagotomy, a procedure in which the vagus nerve is surgically cut, was an experimental technique used in the nineteenth and early twentieth centuries to study the effects of the autonomic nervous system on various organs. For a time, vagotomy was the preferred treatment for stomach ulcers because removal of parasympathetic innervation to the stomach decreased the secretion of stomach acid. However, this procedure had many unwanted side effects and has been abandoned in favor of drug therapies that treat the problem more specifically.

Concept Check

  1. A nerve that carries both sensory and motor information is called a(n)____nerve.

  2. Name the four regions of the spinal cord in order, starting from the brain stem.

The Autonomic Nervous System Uses a Variety of Chemical Signals

Chemically, the sympathetic and parasympathetic branches can be distinguished by their neurotransmitters and receptors, using the following rules and Figure 11.6:

FIG. 11.6 Sympathetic and parasympathetic neurotransmitters and receptors

Figure Question

  1. Identify all:

    1. - cholinergic neurons

    2. - adrenergic neurons

    3. - preganglionic neurons

    4. - postganglionic neurons

  2. Which pathway will have longer preganglionic neurons? (Hint: See Fig. 11.5.)

  1. Both sympathetic and parasympathetic preganglionic neurons release acetylcholine (ACh) onto nicotinic cholinergic receptors (nAChR) on the postganglionic cell [here].

  2. Most postganglionic sympathetic neurons secrete norepinephrine (NE) onto adrenergic receptors on the target cell.

  3. Most postganglionic parasympathetic neurons secrete acetylcholine onto muscarinic cholinergic receptors (mAChR) on the target cell.

However, there are some exceptions to these rules. A few sympathetic postganglionic neurons, such as those that terminate on sweat glands, secrete ACh rather than norepinephrine. These neurons are therefore called sympathetic cholinergic neurons.

A small number of autonomic neurons secrete neither norepinephrine nor acetylcholine and are known as nonadrenergic, noncholinergic neurons. Some of the chemicals they use as neurotransmitters include substance P, somatostatin, vasoactive intestinal peptide (VIP), adenosine, nitric oxide, and ATP. The nonadrenergic, noncholinergic neurons are assigned to either the sympathetic or parasympathetic branch according to where their preganglionic fibers leave the nerve cord.

Autonomic Pathways Control Smooth and Cardiac Muscle and Glands

The targets of autonomic neurons are smooth muscle, cardiac muscle, many exocrine glands, a few endocrine glands, lymphoid tissues, and some adipose tissue. The synapse between a postganglionic autonomic neuron and its target cell is called the neuroeffector junction (recall that targets are also called effectors).

The structure of an autonomic synapse differs from the model synapse [Fig. 8.2f ]. Autonomic postganglionic axons end with a series of swollen areas at their distal ends, like beads spaced out along a string (Fig. 11.7a). Each of these swellings, known as a varicosity {varicosus, abnormally enlarged or swollen}, contains vesicles filled with neurotransmitter.

FIG. 11.7 Autonomic synapses

The branched ends of the axon lie across the surface of the target tissue, but the underlying target cell membrane does not possess clusters of neurotransmitter receptors in specific sites. Instead, the neurotransmitter is simply released into the interstitial fluid to diffuse to wherever the receptors are located. The result is a less-directed form of communication than that which occurs between a somatic motor neuron and a skeletal muscle. The diffuse release of autonomic neurotransmitter means that a single postganglionic neuron can affect a large area of target tissue.

The release of autonomic neurotransmitters is subject to modulation from a variety of sources. For example, sympathetic varicosities contain receptors for hormones and for paracrine signals such as histamine. These modulators may either facilitate or inhibit neurotransmitter release. Some preganglionic neurons co-secrete neuropeptides along with acetylcholine. The peptides act as neuromodulators, producing slow synaptic potentials that modify the activity of postganglionic neurons [here].

Autonomic Neurotransmitters Are Synthesized in the Axon

The primary autonomic neurotransmitters, acetylcholine and norepinephrine, can be synthesized in the axon varicosities (Fig. 11.7b). Both are small molecules easily synthesized by cytoplasmic enzymes. Neurotransmitter made in the varicosities is packaged into synaptic vesicles for storage.

Neurotransmitter release follows the pattern found in other cells: depolarization—calcium signal—exocytosis [here]. When an action potential arrives at the varicosity, voltage-gated Ca2+ channels open, Ca2+ enters the neuron, and the synaptic vesicle contents are released by exocytosis. Once neurotransmitters are released into the synapse, they either diffuse through the interstitial fluid until they encounter a receptor on the target cell or drift away from the synapse.

The concentration of neurotransmitter in the synapse is a major factor in autonomic control of a target: more neurotransmitter means a longer or stronger response. The concentration of neurotransmitter in a synapse is influenced by its rate of breakdown or removal (Fig. 11.7b). Neurotransmitter activation of its receptor terminates when the neurotransmitter (1) diffuses away, (2) is metabolized by enzymes in the extracellular fluid, or (3) is actively transported into cells around the synapse. The uptake of neurotransmitter by varicosities allows neurons to reuse the chemicals.

These steps are shown for norepinephrine in Figure 11.7b. Norepinephrine is synthesized in the varicosity from the amino acid tyrosine. Once released into the synapse, norepinephrine may combine with an adrenergic receptor on the target cell, diffuse away, or be transported back into the varicosity. Inside the neuron, recycled norepinephrine is either repackaged into vesicles or broken down by monoamine oxidase (MAO), the main enzyme responsible for degradation of catecholamines. [See Fig. 8.20 for a similar figure on acetylcholine.]

Table 11.1 compares the characteristics of the two primary autonomic neurotransmitters.

Table 11.1 Postganglionic Autonomic Neurotransmitters

Sympathetic Division Parasympathetic Division
Neurotransmitter Norepinephrine (NE) Acetylcholine (ACh)
Receptor Types α- and β-adrenergic Nicotinic and muscarinic cholinergic
Synthesized from Tyrosine Acetyl CoA + choline
Inactivation Enzyme Monoamine oxidase (MAO) in mitochondria of varicosity Acetylcholinesterase (AChE) in synaptic cleft
Varicosity Membrane Transporters for Norepinephrine Choline

Autonomic Receptors Have Multiple Subtypes

The autonomic nervous system uses only a few neurotransmitters but it diversifies its actions by having multiple receptor subtypes with different second messenger pathways. The sympathetic division has two types of adrenergic receptors with multiple subtypes. The parasympathetic division uses five varieties of muscarinic cholinergic receptors.

Sympathetic Receptors

Sympathetic pathways secrete catecholamines that bind to adrenergic receptors on their target cells. Adrenergic receptors come in two varieties: α (alpha) and β (beta), with several subtypes of each. Alpha receptors—the most common sympathetic receptor—respond strongly to norepinephrine and only weakly to epinephrine (TBL. 11.2).

Table 11.2 Properties of Adrenergic Receptors

Receptor Found in Sensitivity Effect on Second Messenger
*NE = norepinephrine, E = epinephrine
α 1 Most sympathetic target tissues NE > E* Activates phospholipase C
α 2 Gastrointestinal tract and pancreas NE > E Decreases cAMP
β 1 Heart muscle, kidney NE = E Increases cAMP
β 2 Certain blood vessels and smooth muscle of some organs E > NE Increases cAMP
β 3 Adipose tissue NE > E Increases cAMP

The three main subtypes of beta receptors differ in their affinity for catecholamines. β1-receptors respond equally strongly to norepinephrine and epinephrine. β2-receptors are more sensitive to epinephrine than to norepinephrine. Interestingly, the β2-receptors are not innervated (no sympathetic neurons terminate near them), which limits their exposure to the neurotransmitter norepinephrine. β3-receptors, which are found primarily on adipose tissue, are innervated and more sensitive to norepinephrine than to epinephrine.

Adrenergic Receptor Pathways

All adrenergic receptors are G protein-coupled receptors rather than ion channels [here]. This means that the target cell response is slower to start and can persist for a longer time than is usually associated with the nervous system. The long-lasting metabolic effects of some autonomic pathways result from modification of existing proteins or from the synthesis of new proteins.

The different adrenergic receptor subtypes use different second messenger pathways (TBL. 11.2). α1-receptors activate phospholipase C, creating inositol trisphosphate (IP3) and diacylglycerol (DAG) [Fig. 6.8b ]. DAG initiates a cascade that phosphorylates proteins. IP3 opens Ca2+ channels, creating intracellular Ca2+ signals. In general, activation of α 1-receptors causes muscle contraction or secretion by exocytosis. α2-receptors decrease intracellular cyclic AMP and cause smooth muscle relaxation (gastrointestinal tract) or decreased secretion (pancreas).

β-receptors all increase cyclic AMP and trigger the phosphorylation of intracellular proteins. The target cell response then depends on the receptor subtype and the specific downstream pathway in the target cell. For example, activation of β 1- receptors enhances cardiac muscle contraction, but activation of β 2-receptors relaxes smooth muscle in many tissues.

Parasympathetic Pathways

As a rule, parasympathetic neurons release ACh at their targets. As noted earlier, the neuroeffector junctions of the parasympathetic branch have muscarinic cholinergic receptors [here]. Muscarinic receptors are all G protein-coupled receptors. The activation of these receptors initiates second messenger pathways, some of which open K+ or Ca2+ channels. The tissue response to activation of a muscarinic receptor varies with the receptor subtype, of which there are at least five.

Concept Check

  1. In what organelle is most intracellular Ca2+ stored?

  2. What enzyme (a) converts ATP to cAMP? (b) does cAMP activate? [Fig. 6.8a ]

The Adrenal Medulla Secretes Catecholamines

The adrenal medulla {ad-, upon + renal, kidney; medulla, marrow} is a specialized neuroendocrine tissue associated with the sympathetic nervous system. During development, the neural tissue destined to secrete the catecholamines norepinephrine and epinephrine splits into two functional entities: the sympathetic branch of the nervous system, which secretes norepinephrine, and the adrenal medulla, which secretes epinephrine primarily.

The adrenal medulla forms the core of the adrenal glands, which sit atop the kidneys (Fig. 11.8a). Like the pituitary gland, each adrenal gland is actually two glands of different embryological origin that fused during development (Fig. 11.8b). The outer portion, the adrenal cortex, is a true endocrine gland of epidermal origin that secretes steroid hormones [here]. The adrenal medulla, which forms the small core of the gland, develops from the same embryonic tissue as sympathetic neurons and is a neurosecretory structure.

FIG. 11.8 The adrenal medulla

The adrenal medulla is often described as a modified sympathetic ganglion. Preganglionic sympathetic neurons project from the spinal cord to the adrenal medulla, where they synapse (Fig. 11.8c). However, the postganglionic neurons lack the axons that would normally project to target cells. Instead, the axonless cell bodies, called chromaffin cells, secrete the neurohormone epinephrine directly into the blood. In response to alarm signals from the CNS, the adrenal medulla releases large amounts of epinephrine for general distribution throughout the body as part of a fight-or-flight response.

Concept Check

  1. Is the adrenal medulla most like the anterior pituitary or the posterior pituitary? Explain.

  2. Predict whether chromaffin cells have nicotinic or muscarinic ACh receptors.

Autonomic Agonists and Antagonists Are Important Tools in Research and Medicine

The study of the two autonomic branches has been greatly simplified by advances in molecular biology. The genes for many autonomic receptors and their subtypes have been cloned, allowing researchers to create mutant receptors and study their properties. In addition, researchers have either discovered or synthesized a variety of agonist and antagonist molecules (TBL. 11.3). Direct agonists and antagonists combine with the target receptor to mimic or block neurotransmitter action. Indirect agonists and antagonists act by altering secretion, reuptake, or degradation of neurotransmitters.

Table 11.3 Agonists and Antagonists of Neurotransmitter Receptors

Receptor Type Neurotransmitter Agonist Antagonists Indirect Agonists/Antagonists
Cholinergic Acetylcholine AChE* inhibitors: neostigmine
Muscarinic Muscarine Atropine, scopolamine
Nicotinic Nicotine α-bungarotoxin (muscle only), TEA (tetraethylammonium; ganglia only), curare
Adrenergic Norepinephrine (NE), epinephrine Stimulate NE release: ephedrine, amphetamines; Prevents NE uptake: cocaine
Alpha (α) Phenylephrine “Alpha-blockers”
Beta (β) Isoproterenol, albuterol “Beta-blockers”: propranolol (β 1 and β 2), metoprolol (β 1 only)
*AChE = acetylcholinesterase

For example, cocaine is an indirect agonist that blocks the reuptake of norepinephrine into adrenergic nerve terminals, thereby extending norepinephrine’s excitatory effect on the target. This is demonstrated by the toxic effect of cocaine on the heart, where sympathetic-induced vasoconstriction of the heart’s blood vessels can result in a heart attack. Cholinesterase inhibitors, also called anticholinesterases, are indirect agonists that block ACh degradation and extend the active life of each ACh molecule. The toxic organophosphate insecticides, such as parathion and malathion, are anticholinesterases. They kill insects by causing sustained contraction of their breathing muscles so that they are unable to breathe.

Many drugs used to treat depression are indirect agonists that act either on membrane transporters for neurotransmitters (tricyclic antidepressants and selective serotonin reuptake inhibitors) or on their metabolism (monoamine oxidase inhibitors). The older antidepressant drugs that act on norepinephrine transport and metabolism (tricyclics and MAO inhibitors) may have side effects related to their actions in the autonomic nervous system, including cardiovascular problems, constipation, urinary difficulty, and sexual dysfunction {dys-, abnormal or ill}. The serotonin reuptake inhibitors have fewer autonomic side effects. Some of the newest drugs influence the action of both norepinephrine and serotonin.

Many new drugs have been developed from studies of agonists and antagonists. The discovery of α- and β-adrenergic receptors led to the development of drugs that block only one of the two receptor types. The drugs known as beta-blockers have given physicians a powerful tool for treating high blood pressure, one of the most common disorders in the United States today. Early α-adrenergic receptor antagonists had many unwanted side effects, but now pharmacologists can design drugs to target specific receptor subtypes. For example, tamsulosin (Flomax®) blocks alpha-1A adrenergic receptors (ADRA1A) found largely on smooth muscle of the prostate gland and bladder. Relaxing these muscles helps relieve the urinary symptoms of prostatic enlargement.

Primary Disorders of the Autonomic Nervous System Are Relatively Uncommon

Diseases and malfunction of the autonomic nervous system are relatively rare. Direct damage (trauma) to hypothalamic control centers may disrupt the body’s ability to regulate water balance or temperature. Generalized sympathetic dysfunction, or dysautonomia, may result from systemic diseases such as cancer and diabetes mellitus. There are also some conditions, such as multiple system atrophy, in which the CNS control centers for autonomic functions degenerate.

In many cases of sympathetic dysfunction, the symptoms are manifested most strongly in the cardiovascular system, when diminished sympathetic input to blood vessels results in abnormally low blood pressure. Other prominent symptoms of sympathetic pathology include urinary incontinence {in-, unable + continere, to contain}, which is the loss of bladder control, or impotence, which is the inability to achieve or sustain a penile erection.

Occasionally, patients suffer from primary autonomic failure when sympathetic neurons degenerate. In the face of continuing diminished sympathetic input, target tissues up-regulate [here], putting more receptors into the cell membrane to maximize the cell’s response to available norepinephrine. This increase in receptor abundance leads to denervation hypersensitivity, a state in which the administration of exogenous adrenergic agonists causes a greater-than-expected response.

Summary of Sympathetic and Parasympathetic Branches

As you have seen in this discussion, the branches of the autonomic nervous system share some features but are distinguished by others. Many of these features are summarized in Figure 11.9 and compared in Table 11.4.

Table 11.4 Comparison of Sympathetic and Parasympathetic Branches

Sympathetic Parasympathetic
Point of CNS Origin First thoracic to second lumbar segments Midbrain, medulla, and second to fourth sacral segments
Location of Peripheral Ganglia Primarily in paravertebral sympathetic chain; three outlying ganglia located alongside descending aorta On or near target organs
Structure of Region from which Neurotransmitter Is Released Varicosities Varicosities
Neurotransmitter at Target Synapse Norepinephrine (adrenergic neurons) ACh (cholinergic neurons)
Inactivation of Neurotransmitter at Synapse Uptake into varicosity, diffusion Enzymatic breakdown, diffusion
Neurotransmitter Receptors on Target Cells Adrenergic Muscarinic
Ganglionic Synapse ACh on nicotinic receptor ACh on nicotinic receptor
Neuron-Target Synapse NE on α- or β-adrenergic receptor ACh on muscarinic receptor
  1. Both sympathetic and parasympathetic pathways consist of two neurons (preganglionic and postganglionic) in series. One exception to this rule is the adrenal medulla, in which postganglionic sympathetic neurons have been modified into a neuroendocrine organ.

  2. All preganglionic autonomic neurons secrete acetylcholine onto nicotinic receptors. Most sympathetic neurons secrete norepinephrine onto adrenergic receptors. Most parasympathetic neurons secrete acetylcholine onto muscarinic receptors.

  3. Sympathetic pathways originate in the thoracic and lumbar regions of the spinal cord. Parasympathetic pathways leave the CNS at the brain stem and in the sacral region of the spinal cord.

  4. Most sympathetic ganglia are located close to the spinal cord (are paravertebral). Parasympathetic ganglia are located close to or in the target tissue.

  5. The sympathetic branch controls functions that are useful in stress or emergencies (fight-or-flight). The parasympathetic branch is dominant during rest-and-digest activities.