Functional circuits and signal processing in the enteric nervous system

Abstract

The enteric nervous system (ENS) is an extensive network comprising millions of neurons and glial cells contained within the wall of the gastrointestinal tract. The major functions of the ENS that have been most studied include the regulation of local gut motility, secretion, and blood flow. Other areas that have been gaining increased attention include its interaction with the immune system, with the gut microbiota and its involvement in the gut-brain axis, and neuro-epithelial interactions. Thus, the enteric circuitry plays a central role in intestinal homeostasis, and this becomes particularly evident when there are faults in its wiring such as in neurodevelopmental or neurodegenerative disorders. In this review, we first focus on the current knowledge on the cellular composition of enteric circuits. We then further discuss how enteric circuits detect and process external information, how these signals may be modulated by physiological and pathophysiological factors, and finally, how outputs are generated for integrated gut function.

Keywords: Enteric circuitry; Epithelium; Glia; Microbiota; Neuroimmune; Neurons.

Fig. 1

Neuronal components of the enteric circuitry. Intrinsic sensory neurons form interconnected networks encompassing the circumference of the gut wall, and provide extensive innervation of the mucosal epithelium. Within the myenteric plexus (MP), interneurons form chains along the length of the gut, with ascending interneurons projecting orally and descending interneurons projecting anally. Myenteric excitatory and inhibitory motor neurons innervate the circular (CM) and longitudinal muscle (LM), while secretomotor neurons in the submucosal plexus (SMP) project to the mucosa

Fig. 2

Simplified schematic representing the enteric circuitry underlying the peristaltic reflex. Intrinsic sensory neurons synapse with ascending and descending interneurons that form chains along the length of the intestine, as well as excitatory and inhibitory motor neurons. Interneurons also innervate motor neurons which in turn supply the circular and longitudinal muscle (musculature represented by grey lines; note that different muscle layers and their innervation are not defined). Upon detection of a luminal stimulus, the activation of ascending interneurons connected to excitatory motor neurons evoke a contraction orally, while the activation of descending interneurons connected to inhibitory motor neurons elicit a relaxation anally to propel the contents along. Enteric glia also plays an active role in regulating intestinal motility

Fig. 3

Schematic illustrating neurons involved in vasodilator and secretomotor reflexes. Chemical or mechanical stimulation of the mucosa activates myenteric and/or submucosal sensory neurons which then excite secretomotor/vasodilator neurons directly or via interneurons to stimulate secretion and/or vasodilation. Intrinsic sensory neurons may also directly evoke a secretory response via an axon reflex