Enteric Nervous System 1

• ENS


  Network of neuron cell bodies, processes and axons in wall of gastrointestinal tract
• ENS


  • Largest part of ANS
  • Contains more neurons and cell bodies than the spinal cord
• ENS includes axons and terminals of visceral sensory neurons, sympathetic neurons and parasympathetic neurons that innervate the GI tract
• ENS innervates all layers of GI tract including smooth muscle, mucosal epithelium and endocrine cells
• Ganglia


  Clusters of neurons
• Two ganglionated plexuses in ENS

  • Myenteric (Auerbach's) plexus
  • Submucosal (Meissner's) plexus
• Layers of small intestine - ENS

  • Mucosa
  • Mucosal plexus
  • Muscularis mucosae
  • Submucosal plexus
  • Deep muscular plexus
  • Circular muscles
  • Myenteric plexus
  • Longitudinal muscle
• Primary plexus


  Interganglionic connective nerve trunks that run between myenteric ganglia
• Secondary plexus


  Nerve trunks that run into circular muscles
• Tertiary plexus


  Nerve trunks that supply the longitudinal muscles
• Basic properties of ENS

  • Submucosal plexus present in stomach, but not ganglionated
  • Ganglionated submucosal plexus begins at pylorus
  • Ganglionated myenteric plexus begins at upper oesophageal sphincter
  • Several non-ganglionated plexuses
• ENS innervates muscle, mucosa, blood vessels
• A ganglion is a cluster of neuronal cell bodies
• Not all plexuses are ganglionated, some are just nerve trunks that innervate different layers of the GI tract wall
• Myenteric ganglia are typically larger than submucosal ganglia
• Extrinsic Nerve Supply of ENS

  • Sympathetic Nerve
  • Parasympathetic nerves
  • Extrinsic sensory neurons
• Sympathetic nerves


  Innervate whole length of GI tract and modulate enteric nerve circuits
• Parasympathetic nerves


  Primarily innervate upper (oesphagus, stomach, duodenum) and lower (colon, rectum, anus) GI tract, less prominent in jejunum and ileum
• Extrinsic sensory neurons


  Visceral primary afferents that innervate the full length of the GI tract
• Large supply of extrinsic primary afferents to upper GI tract in vagus nerve, 90% of vagal axons are primary afferents
• Dorsal root ganglion cell (spinal) afferents run in splanchnic and pelvic nerves, often thought to be nociceptive
• Functions and central terminations of vagal afferents and dorsal root afferents are distinctively different
• Functions of ENS


  • Controls movement of intestinal content
  • Regulation of water and electrolyte transport across the mucosa
  • Contributes to control of acid secretion in stomach, mucus secretion along length and bicarbonate secretion in duodenum
• Regulation of water and electrolyte transport across the mucosa

  • Movement of water and salt into the body from intestinal lumen – absorption
  • Movement of water and salt from body into lumen – secretion
  • Whole body homeostasis
• Intestinal movements are observed in vitro when GI segments are completely isolated from an organism, indicating that the contractions do not depend on the brain or the spinal cord
• Intestinal contractions are only seen if nutrient is present in the lumen
• Intestinal contractions are abolished by tetrodotoxin, which blocks nerve action potentials, but not those of smooth muscle
• Intestinal contractions are blocked by antagonists of nicotinic or muscarinic acetylcholine receptors
• Intestinal contractions can be confined to a local region or sequentially cover long segments
• The jejunum contains an entire circuit for generation of a complex behaviour involving two types of cholinergic neurons
• Intrinsic sensory neurons in the ENS are sensitive to distension, mucosal deformation and luminal nutrients
• Types of enteric neurons

  • Intrinsic sensory neurons
  • Excitatory motor neurons
  • Inhibitory motor neurons
  • Interneurons
  • Secretomotor neurons
  • Vasodilator neurons
  • Intestinofugal neurons
  • Interplexus interneurons
• Functionally distinct enteric neurons are intermingled, with each ganglion containing over 20 different neuron subtypes
• Enteric neurons can be identified and put into circuits mediating behaviour using a top-down approach, starting with defining the properties specific neurons must have to produce an identified behaviour
• Immunohistochemistry


  Technique that can label for specific neurochemical markers in the ENS, allowing differentiation between different neurochemical subtypes that correlate with certain functional enteric neuronal classes
• Law of the Intestine

  A "physiological" stimulus applied to the intestinal wall will cause a contraction above the stimulus and a relaxation below (ascending excitation and descending inhibition)
• Acetylcholine (ACh) and substance P (SP) each excite the intestinal smooth muscle, and blocking muscarinic ACh receptors reduces ascending excitation leaving a component that is blocked by antagonists of SP receptors
• Inhibition in the muscle appears to be mediated by nitric oxide (NO) and a purine released by the same nerve terminals
• Transcriptomics can identify over 20 different groups of enteric neuron subtypes, but assigning function still depends on projections and physiology
• Properties of intrinsic sensory neurons (ISN)

  • Axon terminals or neurites in or adjacent to sites of physiologically relevant stimulation
  • Output terminals contacting other neurons
  • Respond to physiological stimuli like nutrients without an intervening synapse
  • Express mechanosensitive ion channels