Enteric nervous system

Definitions & Key takeaways

The enteric nervous system (ENS), also known as the intrinsic nervous system, is a division of the autonomic nervous system that controls the gastrointestinal tract. It is a network of more than 100 million nerve cells (neurons) in the wall of the gut, from the esophagus to the anus. The ENS can operate independently from the brain and spinal cord, meaning that you can still digest food even if you're unconscious.

However, it is affected by the parasympathetic nervous system, which promotes digestion; and the sympathetic nervous system, which inhibits digestion. The ENS helps to regulate digestive functions such as digestion, absorption, and motility (movement of food through the gut). It also helps to control blood flow to and from the digestive organs, and t o activate immune cells in the gut.

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Introduction0:00–0:31

The gastrointestinal tract has intrinsic and extrinsic innervation. The intrinsic component is the enteric nervous system and the extrinsic component is the sympathetic and parasympathetic innervation which come from the central nervous system.
The enteric nervous system can function independently to control digestive activities, which is why it’s sometimes called the second brain.
So the parasympathetic input basically enhances digestion, and sympathetic input inhibits digestion. From the esophagus to the anus, the walls of the gastrointestinal tract are lined by the same four layers of tissue.

Gastrointestinal Wall Layers0:31–1:56

The outermost layer is either the adventitia, a thick fibrous connective tissue, or the serosa, a slippery serous membrane.
Next is the muscularis externa, a smooth muscle layer, which contracts automatically, without you even having to think about it.
If we look closer at this muscle layer, it’s actually composed of an inner circular muscle layer, arranged in circular rings which contract and constrict the tract behind the food, which keeps it from moving backward, while the outer longitudinal muscle layer, arranged along the length of the tract, relaxes and lengthens and therefore pulls things forward.
Together, they perform what’s called peristalsis, which is a series of coordinated wave-like muscle contractions that helps squeeze the food bolus in one direction.
In specific places along the tract, like the esophageal sphincter, the circular layer thickens, forming sphincters that keep food from passing from one part of the gastrointestinal tract to the next.
Next is the submucosa, which consists of a dense layer of tissue that contains blood vessels, lymphatics, and nerves. Finally, there’s the inner lining of the intestine called the mucosa which secretes mucus and digestive enzymes because this is the layer that comes into direct contact with food.

Enteric Plexi1:56–2:43

The enteric nervous system is found within the walls of the entire gastrointestinal tract and is made up of two different plexuses.
The submucosal or Meissner’s plexus is found in the submucosa and the myenteric or Auerbach’s plexus, is found within the muscularis externa, between the longitudinal muscle layer and the circular muscle layer.
Each plexus is a weblike formation of neurons that expands throughout the gastrointestinal tract. This web is composed of ganglia which are collections of neurons, and for each ganglion, there are multiple interneurons that connects that ganglia to other ganglia.
Some interneurons even travel from the submucosal plexus to the myenteric plexus to connect the ganglia of the two plexus!
You can think of ganglia like dense cities connected by highways. Now when we eat a hamburger, it gets chewed up and enters the gastrointestinal tract.

Short Reflex2:43–4:02

As it works its way through, the food distends the walls of the gastrointestinal tract, which stimulates mechanoreceptors in the muscularis externa and the mucosa.
The food also increases the levels of protein, fat, sugar in the gastrointestinal tract which stimulates chemoreceptors in the mucosa.
Both mechanoreceptors and chemoreceptors send afferent information through axons that synapse with ganglia in the submucosal plexus.
The information then travels through the plexus from ganglion to ganglion via interneurons. The submucosal ganglia then send signals through efferent fibers that stimulate various glands and enteroendocrine cells that helps with digestion and absorption.
These ganglia also cause blood vessels to vasodilate and that brings increases blood flow to the gastrointestinal tract.
The ganglia in the myenteric plexus are in charge of gastric motility, and they send signals through efferent fibers to the smooth muscles within the circular and longitudinal layers.
This causes an increase in the number and strength of peristaltic contractions. Overall, this is referred to as a short reflex - because both the afferent and efferent components are mediated by the enteric nervous system.

Long Reflex4:02–6:17

Now, the central nervous system can also receive afferent information from, and send efferent information to the gastrointestinal tract via sympathetic and parasympathetic systems, and this is called the long reflex.
When the body is in “rest and digest” mode, the parasympathetic nervous system is active and it enhances digestion. When the body is in “fight or flight” mode, the sympathetic nervous system is active and it inhibits digestion.
In the parasympathetic reflex, the vagus nerve carries afferent sensory information that comes from the upper esophagus to the first ⅓ of the transverse colon, and sends that information to the medulla, where the information is processed.
Afferent sensory information from the rest of the gastrointestinal tract, from the distal ⅔ of of the colon to the rectum, gets carried by the pelvic nerve to the spinal cord.
Efferent parasympathetic stimulation travels along the vagus and pelvic nerve back towards the respective regions of the gastrointestinal tract.
The preganglionic fibers synapse with parasympathetic ganglia within the myenteric and submucosal plexus, and they secrete acetylcholine to stimulate the ganglia.
These ganglia send out postganglionic fibers which secrete either acetylcholine or neuropeptides like substance P or vasoactive intestinal peptides to stimulate smooth muscles, glands, and enteroendocrine cells.
In the sympathetic system, afferent fibers carry signals from the chemo and mechanoreceptors to one of the four sympathetic ganglia - either the celiac, superior mesenteric, inferior mesenteric, or hypogastric ganglia.
These ganglia then send afferent fibers along the greater, lesser, and lumbar splanchnic nerves to the spinal cord where the information is processed.
Preganglionic efferent fibers leave the spinal cord and synapse with one of the sympathetic ganglia where they release acetylcholine.
These ganglia send efferent fibers to smooth muscles, glands, and enteroendocrine cells, just like in the parasympathetic system, except they release norepinephrine which inhibits the target tissue.

Smooth Muscle Contraction6:17–8:50

Now let’s take a closer look at smooth muscle contraction in the gastrointestinal tract. First, there are 2 types of muscle contraction: tonic contractions are continuous, while phasic contractions are the ones where the smooth muscles contract and relax in waves, which causes peristalsis.
Interstitial cells of Cajal, or just Cajal cells, in the myenteric plexus act like pacemaker cells in the heart. Cajal cells generate rhythmic depolarization and repolarization of the cell membrane, called slow wave potentials, without any external stimulation from the neural or endocrine system.
The depolarization of the Cajal cells is caused by the opening of slow sodium channels in the cell membrane which cause an influx of sodium ions, while repolarization is caused by the opening of potassium channels which allows an efflux of potassium.
Cajal cells are connected to smooth muscle cells via gap junctions which allows the slow wave potential to travel through the smooth muscles triggering voltage gated ca2+ (calcium) channels to open, sparking depolarization of the smooth muscle cells.
Now, slow wave potentials cause relatively weak depolarizations, which don’t reach the threshold potential needed to cause peristaltic contractions.
However they are strong enough to cause weak tonic contraction which maintains the tone of the gastrointestinal tract. Now, action potentials from the extrinsic nervous system also cause depolarization of the smooth muscle cells by opening up a different set of voltage gated ca2+ channels.
When these extrinsically triggered depolarizations are combined with the slow wave depolarizations, it reaches the threshold potential needed to trigger peristaltic contractions.
So basically, slow wave potentials from the enteric nervous system cause tonic contractions, while slow waves potentials plus action potentials from the extrinsic nervous system cause peristaltic contractions.
The number of action potentials on top of each slow wave correlates to the strength of the contraction. That means that the extrinsic innervation of the gastrointestinal tract can modify the strength of each contraction, but the rate of the contraction is determined by the rate of the slow waves.
Different sections of the gastrointestinal tract have their own unique slow wave frequency. For example, the stomach has the lowest rate at about 3 slow waves per minute, whereas the duodenum has the highest rate at 12 slow waves per minute.

Review8:50–9:24

Alright, as a quick recap, the enteric nervous system, also called the intrinsic nervous system can operate autonomously.
But it’s affected by the parasympathetic nervous system which promotes digestion, and the sympathetic nervous system which inhibits digestion.
Slow waves from the enteric nervous system cause the tonic contraction of the gastrointestinal tract, whereas the peristaltic contractions require both the slow wave and extrinsic innervation.
Slow waves determine the rate of contraction, but the extrinsic innervation can modify the strength of contraction.