Autonomic nervous system

Autonomic nervous system
Latin	divisio autonomica systematis nervosi peripherici

The autonomic nervous system (ANS or visceral nervous system or involuntary nervous system) is the part of the peripheral nervous system that acts as a control system, functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiratory rate, salivation, perspiration, pupillary dilation, micturition (urination), and sexual arousal. Most autonomous functions are involuntary but a number of ANS actions can work alongside some degree of conscious control. Everyday examples include breathing, swallowing, and sexual arousal, and in some cases functions such as heart rate.

Within the brain, the ANS is located in the medulla oblongata in the lower brainstem. The medulla's major ANS functions include respiration (the respiratory control centre, or "rcc"), cardiac regulation (the cardiac control centre, or "ccc"), vasomotor activity (the vasomotor centre or "vmc"), and certain reflex actions (such as coughing, sneezing, vomiting and swallowing). These then subdivide into other areas and are also linked to ANS subsystems and nervous systems external to the brain. The hypothalamus, just above the brain stem, acts as an integrator for autonomic functions, receiving ANS regulatory input from the limbic system to do so.

The ANS is classically divided into two subsystems: the parasympathetic nervous system (PSNS) and sympathetic nervous system (SNS) which operate independently in some functions and interact co-operatively in others. In many cases the two have "opposite" actions where one activates a physiological response and the other inhibits it. An older simplification of the sympathetic and parasympathetic nervous systems as "excitory" and "inhibitory" was overturned due to the many exceptions found. A more modern characterisation is that the sympathetic nervous system is a "quick response mobilising system" and the parasympathetic is a "more slowly activated dampening system", but even this has exceptions, such as in sexual arousal and orgasm where both play a role. The enteric nervous system is also sometimes considered part of the autonomic nervous system, and sometimes considered an independent system.

ANS functions can generally be divided into sensory (afferent) and motor (efferent) subsystems. Within both there are inhibitory and excitatory synapses between neurons. Relatively recently, a third subsystem of neurons that have been named 'non-adrenergic and non-cholinergic' neurons (because they use nitric oxide as a neurotransmitter) have been described and found to be integral in autonomic function, particularly in the gut and the lungs.

Anatomy

ANS innervation is divided into sympathetic nervous system and parasympathetic nervous system divisions. The sympathetic division has thoracolumbar “outflow”, meaning that the neurons begin at the thoracic and lumbar (T1-L2/3) portions of the spinal cord. The parasympathetic division has craniosacral “outflow”, meaning that the neurons begin at the cranial nerves (CN 3, CN7, CN 9, CN10) and sacral (S2-S4) spinal cord.

The ANS is unique in that it requires a sequential two-neuron efferent pathway; the preganglionic neuron must first synapse onto a postganglionic neuron before innervating the target organ. The preganglionic, or first, neuron will begin at the “outflow” and will synapse at the postganglionic, or second, neuron’s cell body. The postganglionic neuron will then synapse at the target organ.

Sympathetic division

The sympathetic division (thoracolumbar outflow) consists of cell bodies in the lateral horn of the spinal cord (intermediolateral cell columns) from T1 to L2/3. These cell bodies are GVE (general visceral efferent) neurons and are the preganglionic neurons. There are several locations upon which preganglionic neurons can synapse for their postganglionic neurons:

• Paravertebral ganglia (3) of the sympathetic chain (these run on either side of the vertebral bodies)

1. cervical ganglia (3)
2. thoracic ganglia (12) and rostral lumbar ganglia (2 or 3)
3. caudal lumbar ganglia and pelvic ganglia

• Prevertebral ganglia (celiac ganglion, aorticorenal ganglion, superior mesenteric ganglion, inferior mesenteric ganglion)
• Chromaffin cells of the adrenal medulla (this is the one exception to the two-neuron pathway rule: the synapse is directly efferent onto the target cell bodies)

These ganglia provide the postganglionic neurons from which innervation of target organs follows. Examples of splanchnic (visceral) nerves are:

• Cervical cardiac nerves & thoracic visceral nerves which synapse in the sympathetic chain
• Thoracic splanchnic nerves (greater, lesser, least) which synapse in the prevertebral ganglion
• Lumbar splanchnic nerves which synapse in the prevertebral ganglion
• Sacral splanchnic nerves which synapse in the inferior hypogastric plexus

These all contain afferent (sensory) nerves as well, known as GVA (general visceral afferent) neurons.

Parasympathetic division

The parasympathetic division (craniosacral outflow) consists of cell bodies from one of two locations: the brainstem (Cranial Nerves III, VII, IX, X) or the sacral spinal cord (S2, S3, S4). These are the preganglionic neurons, which synapse with postganglionic neurons in these locations:

• Parasympathetic ganglia of the head (Ciliary (CN III), Submandibular (CN VII), Pterygopalatine (CN VII), or Otic (CN IX) nerves)
• In or near the wall of an organ innervated by the Vagus (CN X) or Sacral nerves (S2, S3, S4))

These ganglia provide the postganglionic neurons from which innervations of target organs follows. Examples are:

• The preganglionic parasympathetic splanchnic (visceral) nerves
• The Vagus Nerve, which wanders through the thorax and abdominal regions innervating, among other organs, the heart, lungs, liver and stomach

Sensory neurons

Main article: Sensory neuron

The sensory arm is made of “primary visceral sensory neurons” found in the peripheral nervous system (PNS), in “cranial sensory ganglia”: the geniculate, petrosal and nodose ganglia, appended respectively to cranial nerves VII, IX and X. These sensory neurons monitor the levels of carbon dioxide, oxygen and sugar in the blood, arterial pressure and the chemical composition of the stomach and gut content. They also convey the sense of taste and smell which, unlike most functions of the ANS, is a conscious perception. Blood oxygen and carbon dioxide are in fact directly sensed by the carotid body, a small collection of chemosensors at the bifurcation of the carotid artery, innervated by the petrosal (IXth) ganglion. Primary sensory neurons project (synapse) onto “second order” or relay visceral sensory neurons located in the medulla oblongata, forming the nucleus of the solitary tract (nTS), that integrates all visceral information. The nTS also receives input from a nearby chemosensory center, the area postrema, that detects toxins in the blood and the cerebrospinal fluid and is essential for chemically induced vomiting or conditional taste aversion (the memory that ensures that an animal which has been poisoned by a food never touches it again). All this visceral sensory information constantly and unconsciously modulates the activity of the motor neurons of the ANS.

Motor neurons

Main article: Motor neuron

Motor neurons of the ANS are also located in ganglia of the PNS, called “autonomic ganglia.” They belong to three categories with different effects on their target organs (see below “Function”): sympathetic, parasympathetic and enteric.

Sympathetic ganglia are located in two sympathetic chains close to the spinal cord: the prevertebral and pre-aortic chains. Parasympathetic ganglia, in contrast, are located in close proximity to the target organ: the submandibular ganglion close to salivary glands, paracardiac ganglia close to the heart, etc. Enteric ganglia, which as their name implies innervate the digestive tube, are located inside its walls and collectively contain as many neurons as the entire spinal cord, including local sensory neurons, motor neurons and interneurons. It is the only truly autonomous part of the ANS and the digestive tube can function surprisingly well even in isolation. For that reason the enteric nervous system has been called “the second brain.”

The activity of autonomic ganglionic neurons is modulated by “preganglionic neurons” (also called, improperly but classically, "visceral motoneurons") located in the central nervous system. Preganglionic sympathetic neurons are in the spinal cord, at thoraco-lumbar levels. Preganglionic parasympathetic neurons are in the medulla oblongata (forming visceral motor nuclei: the dorsal motor nucleus of the vagus nerve (dmnX), the nucleus ambiguus, and the salivatory nuclei), and in the sacral spinal cord. Enteric neurons are also modulated by input from the CNS and from preganglionic neurons located, like parasympathetic ones, in the medulla oblongata (in the dmnX).

The feedback from the sensory to the motor arm of visceral reflex pathways is provided by direct or indirect connections between the nucleus of the solitary tract and the visceral motor neurons.

Function

Sympathetic and parasympathetic divisions typically function in opposition to each other. But this opposition is better termed complementary in nature rather than antagonistic. For an analogy, one may think of the sympathetic division as the accelerator and the parasympathetic division as the brake. The sympathetic division typically functions in actions requiring quick responses. The parasympathetic division functions with actions that do not require immediate reaction. The sympathetic system is often considered the "fight or flight" system, while the parasympathetic system is often considered the "rest and digest" or "feed and breed" system.

However, many instances of sympathetic and parasympathetic activity cannot be ascribed to "fight" or "rest" situations. For example, standing up from a reclining or sitting position would entail an unsustainable drop in blood pressure if not for a compensatory increase in the arterial sympathetic tonus. Another example is the constant, second to second, modulation of heart rate by sympathetic and parasympathetic influences, as a function of the respiratory cycles. More generally, these two systems should be seen as permanently modulating vital functions, in usually antagonistic fashion, to achieve homeostasis. Some typical actions of the sympathetic and parasympathetic systems are listed below.

Sympathetic nervous system

Main article: Sympathetic nervous system

Promotes a "fight or flight" response, corresponds with arousal and energy generation, and inhibits digestion.

• Diverts blood flow away from the gastro-intestinal (GI) tract and skin via vasoconstriction.
• Blood flow to skeletal muscles and the lungs is enhanced (by as much as 1200% in the case of skeletal muscles).
• Dilates bronchioles of the lung, which allows for greater alveolar oxygen exchange.
• Increases heart rate and the contractility of cardiac cells (myocytes), thereby providing a mechanism for enhanced blood flow to skeletal muscles.
• Dilates pupils and relaxes the ciliary muscle to the lens, allowing more light to enter the eye and far vision.
• Provides vasodilation for the coronary vessels of the heart.
• Constricts all the intestinal sphincters and the urinary sphincter.
• Inhibits peristalsis.
• Stimulates orgasm.

Parasympathetic nervous system

Main article: Parasympathetic nervous system

Promotes a "rest and digest" response, promotes calming of the nerves return to regular function, and enhances digestion.

• The parasympathetic nerves dilate blood vessels leading to the GI tract, increasing blood flow. This is important following the consumption of food, due to the greater metabolic demands placed on the body by the gut.
• The parasympathetic nervous system can also constrict the bronchiolar diameter when the need for oxygen has diminished.
• Dedicated cardiac branches of the Vagus and thoracic Spinal Accessory nerves impart Parasympathetic control of the Heart or Myocardium.
• During accommodation, the parasympathetic nervous system causes constriction of the pupil and contraction of the ciliary muscle to the lens, allowing for closer vision.
• The parasympathetic nervous system stimulates salivary gland secretion, and accelerates peristalsis, so, in keeping with the rest and digest functions, appropriate PNS activity mediates digestion of food and indirectly, the absorption of nutrients.
• The PNS is also involved in the erection of genital tissues, via the pelvic splanchnic nerves 2–4.
• The PNS is responsible for stimulating sexual arousal.

Neurotransmitters and pharmacology

At the effector organs, sympathetic ganglionic neurons release noradrenaline (norepinephrine), along with other cotransmitters such as ATP, to act on adrenergic receptors, with the exception of the sweat glands and the adrenal medulla:

• Acetylcholine is the preganglionic neurotransmitter for both divisions of the ANS, as well as the postganglionic neurotransmitter of parasympathetic neurons. Nerves that release acetylcholine are said to be cholinergic. In the parasympathetic system, ganglionic neurons use acetylcholine as a neurotransmitter to stimulate muscarinic receptors.
• At the adrenal medulla, there is no postsynaptic neuron. Instead the presynaptic neuron releases acetylcholine to act on nicotinic receptors. Stimulation of the adrenal medulla releases adrenaline (epinephrine) into the bloodstream which acts on adrenoceptors, producing a widespread increase in sympathetic activity.

The following table reviews the actions of these neurotransmitters as a function of their receptors.

Circulatory system

Heart

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
cardiac output	β1, (β2): increases	M2: decreases
SA node: heart rate (chronotropic)	β1, (β2): increases	M2: decreases
Atrial cardiac muscle: contractility (inotropic)	β1, (β2): increases	M2: decreases
at AV node	β1: increases conduction increases cardiac muscle automaticity	M2: decreases conduction Atrioventricular block
Ventricular cardiac muscle	β1, (β2): increases contractility (inotropic) increases cardiac muscle automaticity	---

Blood vessels

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
vascular smooth muscle in general	α1: contracts; β2: relaxes	M3: relaxes
renal artery	α1: constricts	---
larger coronary arteries	α1 and α2: constricts	---
smaller coronary arteries	β2:dilates	---
arteries to viscera	α: constricts	---
arteries to skin	α: constricts	---
arteries to brain	α1: constricts	---
arteries to erectile tissue	α1: constricts	M3: dilates
arteries to salivary glands	α: constricts	M3: dilates
hepatic artery	β2: dilates	---
arteries to skeletal muscle	β2: dilates	---
Veins	α1 and α2: constricts β2: dilates	---

Other

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
platelets	α2: aggregates	---
mast cells - histamine	β2: inhibits	---

Respiratory system

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
smooth muscles of bronchioles	β2: relaxes (major contribution) α1: contracts (minor contribution)	M3: contracts

The bronchioles have no sympathetic innervation, but are instead affected by circulating adrenaline

Visual System

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
Pupil dilator muscle	α1: Dilates (causes mydriasis)
Iris sphincter muscle	-	M3: contracts (causes miosis)
Ciliary muscle	β2: relaxes (causes long-range focus)	M3: contracts (causes short-range focus)

Digestive system

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
salivary glands: secretions	β: stimulates viscous, amylase secretions α1: stimulates potassium secretions	M3: stimulates watery secretions
lacrimal glands (tears)	β: stimulates protein secretion	---
juxtaglomerular apparatus of kidney	β1: renin secretion	---
parietal cells	---	M1: Gastric acid secretion
liver	α1, β2: glycogenolysis, gluconeogenesis	---
adipose cells	β1, β3: stimulates lipolysis	---
GI tract (smooth muscle) motility	α1, α2, β2: decreases	M3, (M1): increases
sphincters of GI tract	α1, α2, β2: contracts	M3: relaxes
glands of GI tract	no effect	M3: secretes

Endocrine system

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
pancreas (islets)	α2: decreases insulin secretion from beta cells, increases glucagon secretion from alpha cells	M3: increases secretion of both insulin and glucagon.
adrenal medulla	N (nicotinic ACh receptor): secretes epinephrine and norepinephrine	---

Urinary system

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
Detrusor urinae muscle of bladder wall	β2, β3: relaxes	M3: contracts
internal urethral sphincter	α1: contracts	M3: relaxes

Reproductive system

Target	Sympathetic (adrenergic)	Parasympathetic (muscarinic)
uterus	α1: contracts (pregnant) β2: relaxes (non-pregnant)	---
genitalia	α1: contracts (ejaculation)	M3: erection

Integumentary system

Target	Sympathetic (muscarinic and adrenergic)	Parasympathetic
sweat gland secretions	M: stimulates (major contribution); α1: stimulates (minor contribution)	---
arrector pili	α1: stimulates	---

External links

• Receptors of the heart: Mnemonic
• ANS Medical Notes on rahulgladwin.com
• Explanations on the ANS by Dyansys, Inc.