The enteric nervous system (ENS) or intrinsic nervous system is one of the main divisions of the

autonomic nervous system The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the peripheral nervous system that supplies internal organs, smooth muscle and glands. The autonomic nervous system is a control system t ...

(ANS) and consists of a mesh-like system of

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa ...

s that governs the function of the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

. It is capable of acting independently of the sympathetic and

parasympathetic nervous system The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part o ...

s, although it may be influenced by them. The ENS is nicknamed the "second brain". It is derived from

neural crest Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...

cells. The enteric nervous system is capable of operating independently of the brain and spinal cord, but does rely on innervation from the

vagus nerve The vagus nerve, also known as the tenth cranial nerve, cranial nerve X, or simply CN X, is a cranial nerve that interfaces with the parasympathetic control of the heart, lungs, and digestive tract. It comprises two nerves—the left and righ ...

and prevertebral ganglia in healthy subjects. However, studies have shown that the system is operable with a severed vagus nerve. The neurons of the enteric nervous system control the motor functions of the system, in addition to the secretion of gastrointestinal enzymes. These neurons communicate through many

neurotransmitters A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neurot ...

similar to the CNS, including

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...

, and

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

. The large presence of serotonin and dopamine in the gut are key areas of research for neurogastroenterologists.

Structure

2402 Layers of the Gastrointestinal Tract

The enteric nervous system in humans consists of some 500 million

s (including the various types of Dogiel cells), 0.5% of the number of neurons in the

brain A brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as Visual perception, vision. I ...

, five times as many as the one hundred million neurons in the human spinal cord, and about as many as in the whole nervous system of a cat. The enteric nervous system is embedded in the lining of the

gastrointestinal system The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

, beginning in the esophagus and extending down to the anus. The neurons of the ENS are collected into two types of

ganglia A ganglion is a group of neuron cell bodies in the peripheral nervous system. In the somatic nervous system this includes dorsal root ganglia and trigeminal ganglia among a few others. In the autonomic nervous system there are both sympathe ...

: myenteric (Auerbach's) and submucosal (Meissner's) plexuses. Myenteric plexuses are located between the inner and outer layers of the

muscularis externa The muscular layer (muscular coat, muscular fibers, muscularis propria, muscularis externa) is a region of muscle in many organs in the vertebrate body, adjacent to the submucosa. It is responsible for gut movement such as peristalsis. The Latin, ...

, while submucosal plexuses are located in the

submucosa The submucosa (or tela submucosa) is a thin layer of tissue in various organs of the gastrointestinal, respiratory, and genitourinary tracts. It is the layer of dense irregular connective tissue that supports the mucosa (mucous membrane) and j ...

Auerbach's plexus

Auerbach's plexus, also known as the myenteric plexus, is a collection of unmyelinated fibers and postganglionic autonomic cell bodies that lie between the circular and longitudinal layers of the muscularis externa in the gastrointestinal tract. It was discovered and named by German neuropathologist

Leopold Auerbach Leopold Auerbach (27 April 1828 – 30 September 1897) was a German anatomist and neuropathologist born in Breslau. Education and career Auerbach studied medicine at the Universities of Breslau, Berlin and the Leipzig. He became a physician in ...

. These neurons provide motor inputs to both layers of the muscularis externa and provide both parasympathetic and sympathetic input. The anatomy of the plexus is similar to the anatomy of the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

. The plexus includes sensory receptors, such as

chemoreceptors A chemoreceptor, also known as chemosensor, is a specialized sensory receptor which transduces a chemical substance (endogenous or induced) to generate a biological signal. This signal may be in the form of an action potential, if the chemorecept ...

and

mechanoreceptors A mechanoreceptor, also called mechanoceptor, is a sensory receptor that responds to mechanical pressure or distortion. Mechanoreceptors are innervated by sensory neurons that convert mechanical pressure into electrical signals that, in animals, a ...

, that are used to provide sensory input to the interneurons in the enteric nervous system. The plexus is the parasympathetic nucleus of origin for the vagus nerve and communicates with the

medulla oblongata The medulla oblongata or simply medulla is a long stem-like structure which makes up the lower part of the brainstem. It is anterior and partially inferior to the cerebellum. It is a cone-shaped neuronal mass responsible for autonomic (invol ...

through both the anterior and posterior vagal nerves.

Submucosal plexus

The submucosal plexus (also known as Meissner's plexus) is found in the submucosal layer of the

. It was discovered and named by German physiologist

Georg Meissner George Meissner (19 November 1829 – 30 March 1905) was a German anatomist and physiologist born in Hanover. He studied medicine at the University of Göttingen, where he worked closely with Rudolf Wagner (1806–1864). In 1851 he accompa ...

. It functions as a pathway for the innervation in the mucosa layer of the gastrointestinal wall.

Function

The ENS is capable of autonomous functions like the coordination of

reflex In biology, a reflex, or reflex action, is an involuntary, unplanned sequence or action and nearly instantaneous response to a stimulus. Reflexes are found with varying levels of complexity in organisms with a nervous system. A reflex occurs ...

es; although it receives considerable innervation from the autonomic nervous system, it can and does operate independently of the brain and the spinal cord. Its study is the focus of neurogastroenterology.

Complexity

The enteric nervous system has been described as a "second brain" for several reasons. The enteric nervous system can operate autonomously. It normally communicates with the

(CNS) through the

parasympathetic The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of ...

(e.g., via the

) and sympathetic (e.g., via the prevertebral ganglia) nervous systems. However,

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with ...

studies show that when the

is severed, the enteric nervous system continues to function. In vertebrates, the enteric nervous system includes

efferent neurons Efferent nerve fibers refer to axonal projections that ''exit'' a particular region; as opposed to afferent projections that ''arrive'' at the region. These terms have a slightly different meaning in the context of the peripheral nervous syste ...

, afferent neurons, and

interneurons Interneurons (also called internuncial neurons, relay neurons, association neurons, connector neurons, intermediate neurons or local circuit neurons) are neurons that connect two brain regions, i.e. not direct motor neurons or sensory neurons. I ...

, all of which make the enteric nervous system capable of carrying reflexes and acting as an integrating center in the absence of CNS input. The sensory neurons report on mechanical and chemical conditions. Through intestinal muscles, the motor neurons control

peristalsis Peristalsis ( , ) is a radially symmetrical contraction and relaxation of muscles that propagate in a wave down a tube, in an anterograde direction. Peristalsis is progression of coordinated contraction of involuntary circular muscles, whi ...

and churning of intestinal contents. Other neurons control the secretion of

enzymes Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...

. The enteric nervous system also makes use of more than 30

, most of which are identical to the ones found in CNS, such as

, and

. More than 90% of the body's serotonin lies in the gut, as well as about 50% of the body's dopamine, which is currently being studied to further our understanding of its utility in the brain. The enteric nervous system has the capacity to alter its response depending on such factors as bulk and nutrient composition. In addition, the ENS contains support cells which are similar to

astroglia Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of end ...

of the brain and a diffusion barrier around the capillaries surrounding ganglia which is similar to the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of the central nervous system where ne ...

of cerebral blood vessels.

Peristalsis

Peristalsis is a series of radially symmetrical contractions and relaxations of muscles which propagate down a muscular tube. In humans and other mammals, peristalsis is found in the smooth muscles of the digestive tract to propel contents through the digestive system. The word is derived from New Latin and comes from the Greek peristallein, "to wrap around," from peri-, "around" + stallein, "to place". Peristalsis was discovered in 1899 by the work of physiologists

William Bayliss Sir William Maddock Bayliss (2 May 1860 – 27 August 1924) was an English physiologist. Life He was born in Wednesbury, Staffordshire but shortly thereafter his father, a successful merchant of ornamental ironwork, moved his family to a ...

and

Ernest Starling Ernest Henry Starling (17 April 1866 – 2 May 1927) was a British physiologist who contributed many fundamental ideas to this subject. These ideas were important parts of the British contribution to physiology, which at that time led the world ...

. Working on the

small intestines The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the pa ...

of dogs, they found that the response of increasing the pressure in the intestine caused the contraction of the muscle wall above the point of stimulation and the relaxation of the muscle wall below the point of stimulation.

Segmentation

Segmentation contractions are the contractions in intestines carried out by the smooth muscle walls. Unlike peristalsis, which involves the contraction and relaxation of muscles in one direction, segmentation occurs simultaneously in both directions as the circular muscles alternatively contract. This allows for thorough mixing of intestinal contents, known as

chyme Chyme or chymus (; from Greek χυμός ''khymos'', "juice") is the semi-fluid mass of partly digested food that is expelled by a person's stomach, through the pyloric valve, into the duodenumgastrointestinal hormones, such as

gastrin Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas. Gast ...

and

secretin Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the du ...

, is regulated through cholinergic neurons residing in the walls of the digestive tract. Hormone secretion is controlled by the

vagovagal reflex Vagovagal reflex refers to gastrointestinal tract reflex circuits where afferent and efferent fibers of the vagus nerve coordinate responses to gut stimuli via the dorsal vagal complex in the brain. The vagovagal reflex controls contraction of ...

, where the neurons in the digestive tract communicate through both afferent and efferent pathways with the

Clinical significance

Neurogastroenterology encompasses the study of the brain, the gut, and their interactions with relevance to the understanding and management of gastrointestinal

motility Motility is the ability of an organism to move independently, using metabolic energy. Definitions Motility, the ability of an organism to move independently, using metabolic energy, can be contrasted with sessility, the state of organisms th ...

and functional gastrointestinal disorders. Specifically, neurogastroenterology focuses on the functions, malfunctions, and the malformations of the sympathetic,

, and enteric divisions of the digestive tract. The term also describes a medical sub-specialism of gastroenterology dedicated to the treatment of motility and functional gastrointestinal disorders.

Functional gastrointestinal disorders

Functional gastrointestinal (GI) disorders are a class of gastrointestinal disorders where there is a malfunction in the normal activities of the gastrointestinal tract, but there are no structural abnormalities that can explain the cause. There are rarely any tests that can detect the presence of these disorders. Clinical research in neurogastroenterology focuses mainly on the study of common functional gastrointestinal disorders such as

irritable bowel syndrome Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ...

, the most common functional GI disorder.

Motility disorders

Motility disorders are the second classification of gastrointestinal disorder studied by neurogastroenterologists. Motility disorders are divided by what they affect, with four regions: The esophagus, the stomach, the small intestines, and the large intestines. Clinical research in neurogastroenterology focuses mainly on the study of common motility disorders such as

gastroesophageal reflux disease Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...

, the damage of the mucosa of the esophagus caused by rising stomach acid through the lower esophageal sphincter.

Gut ischaemia

ENS function can be damaged by

ischemia Ischemia or ischaemia is a restriction in blood supply to any tissue, muscle group, or organ of the body, causing a shortage of oxygen that is needed for cellular metabolism (to keep tissue alive). Ischemia is generally caused by problems w ...

. Transplantation, previously described as a theoretical possibility, has been a clinical reality in the United States since 2011 and is regularly performed at some hospitals.

Additional images

Image:Gray1071.png, The myenteric plexus of a rabbit. X 50. Image:Gray1072.png, The submucosal plexus of a rabbit. X 50.

Neurogastroenterology societies

* American Neurogastroenterology and Motility Society *

European Society of Neurogastroenterology and Motility The European Society of Neurogastroenterology & Motility (ESNM) is a professional medical non-profit organization that was founded in 1982. The ESNM has over 3,100 European members, who are involved in the study of neuroscience and the pathophysiolo ...

ESNM - European Society for Neurogastroenterology & Motility
/ref> ** '' Neurogastroenterology & Motility''

References

Further references

* Grosell M, Farrell A P and Brauner C J (Eds) (2010
''Fish Physiology: The Multifunctional Gut of Fish''
Academic Press. . * Gershon M. D. (1999), ''The Second Brain: A Groundbreaking New Understanding of Nervous Disorders of the Stomach and Intestine'', Harper Perennial, .

External links

* {{DEFAULTSORT:Enteric Nervous System Animal anatomy