Figure 4.

Schematic representation of the enteric neural circuitry underlying the neural control of the circular muscle (the main driving force for propulsion). Intrinsic primary afferent neurons synapse with ascending and descending interneurons that run along the length of the intestine, which then activate excitatory (orally) and inhibitory (anally) motor neurons. Upon a chemical or mechanical luminal stimulus, intrinsic primary afferent neurons cause the activation of ascending interneurons that synapse with excitatory motor neurons evoking an oral contraction, whereas the activation of descending interneurons leads to the excitation of inhibitory motor neurons eliciting a relaxation anally. This polarized reflex circuitry allows for a pressure gradient to be developed that propels the contents anally. The primary transmitters involved include acetylcholine (ACh) for all of the pathways except for inhibitory motor neurons that use nitric oxide and purine nucleotides as their primary neurotransmitters. Substance P (SP) or a related tachykinin provides an important adjunct to the excitatory innervation of smooth muscle; likewise, vasoactive intestinal peptide (VIP) is an adjunct to the inhibitory innervation of smooth muscle. Enteric glia also play an active role in regulating intestinal motility. Neuronal recruitment in the descending circuitry is subject to glial inhibitory control in a muscarinic M3-dependent manner. Enteric glial purinergic signaling preferentially stimulates neuronal responses within the ascending circuitry, which may also be under inhibitory regulation (see Ref. 85 for details). Image created with BioRender.com, with permission.