Characteristics of mucosally projecting myenteric neurones in the guinea‐pig proximal colon

Abstract

Neural regulation of a variety of gastrointestinal functions is primarily achieved by the enteric nervous system which is embedded within the gastrointestinal wall. It is usually formed from two major plexus: the myenteric plexus located between the circular and the longitudinal muscle layer and the submucosal plexus situated between the submucosa and the mucosa (for review, see Wood, 1994). In the early part of the 1970s, the first attempt to classify enteric neurones was made using extracellular recording techniques (Wood, 1970). Nishi & North (1973) and Hirst et al. (1974) then used intracellular microelectrode techniques to determine the electrophysiological characteristics of myenteric neurones in the guinea-pig small intestine. Although their classification schemes did not recover exactly the same neuronal populations, two major groups of neurones were revealed. Following the classification of Hirst et al. (1974), S neurones (for synaptically driven) and AH neurones (named after the characteristic long-lasting membrane potential hyperpolarization following the action potential) made up the two populations. Further studies by Wood and his collaborators revealed the presence of different classes of myenteric neurones depending on the region of the gut studied (Wood, 1994). Additionally, enteric neurones may be subdivided into neurochemically distinct populations (Costa et al. 1996), whose number exceeds the broadly defined electrophysiological classes. The use of intracellular injection of biocytin or neurobiotin allowed the morphology of electrophysiologically classified neurones to be determined. AH neurones were extensively studied in the ileum (for review, see Furness et al. 1998) where they were shown to have morphological characteristics of multipolar Dogiel type II neurones with most processes projecting in the circumferential direction (Iyer et al. 1988;Bornstein et al. 1991). Neuronal tracing methods showed

Relationship between postsynaptic NK1 receptor distribution and nerve terminals innervating myenteric neurons in the guinea‐pig ileum

“…These data suggest that tachykinins might be transmitters at synapses in the ganglia. Consistent with this are pharmacological studies in which a block of NK 1 or NK 3 receptors has antagonised neuro-neuronal transmission in enteric ganglia (Mawe, 1995;Johnson et al, 1998;Frieling et al, 1999;Neunlist et al, 1999). At the light microscope level, NK 1 receptors appear to be evenly distributed over the surfaces of nerve cells.…”

Effects of PGE2 in guinea pig colonic myenteric ganglia

“…S cell depolarization in response to acute PGE 2 application was also inhibited by TTX, suggesting that PGE 2 also depolarizes S cells through direct and indirect mechanisms. S cells exhibit Dogiel type I morphology with single axonal processes that typically contact the circular or longitudinal muscle bundles, but S/Dogiel type I cells do not exhibit processes that extend into the lamina propria (10,35,40,54). It is therefore unlikely that S cells are directly altered by the inflammatory response in colitis, but their activity may change due to upstream changes in the neuronal reflex circuitry.…”

“…Because AH cells are thought to act as intrinsic primary afferent neurons and interneurons in the motor reflex circuitry of the intestines, alteration of active and passive membrane properties of AH cells would affect the afferent portion of the peristaltic reflex arc (35,40). AH cells have processes that extend into the lamina propria, as well as projections to other myenteric neurons (2)(3)(4)40). Thus, because the inflammatory response is typically centered in the lamina propria of the mucosal layer in colitis, the processes of AH cells would be directly exposed to proinflammatory mediators such as PGE 2 .…”

“…30). These cells have a Dogiel type II morphology (multiple processes) and extend projections to other ganglia and to the lamina propria (7,34,40,42), where they could respond to stimuli originating at the mucosal surface. Therefore, changes in the electrical properties of AH cells would likely alter motility and secretory patterns in the gut.…”

Gut chemosensing mechanisms

“…However, the fact that mucosal ENS innervation does not extend to the gut lumen implies that enteric neurons are predominantly exposed to absorbed nutrients and local metabolic products. FFAR3 has been detected in submucosal and myenteric ganglia (107) and may underlie actions of SCFAs on enteric neuronal activity (144)(145)(146). Counterstaining with antibodies against VIP revealed co-localization with FFAR3, indicating that SCFAs may be sensed by secretomotor neurons involved in the regulation of water and electrolyte secretion (107).…”