The enteric nervous system (ENS) represents theintrinsic nervous system of the GI tract and is present along its entire length. The ENS is one of the largest and more complexcomponents of the peripheral nervous system and organized as plexuses of interconnected ganglia that enmesh the GI tract. In the small and large intestine, these plexuses are present in two distinct layers, the outer myenteric plexus that sits between the inner circular and outer longitudinal muscle layers and the inner submucosal plexus present between the mucosa and the inner circular muscle layer. The ENS comprises neurons and glia organized into aggregates of cell bodies organglia . These are interconnected by bundles of nerve fibers that run along the individual plexuses as well as those that run between them. The real complexity of the ENS is revealed at the ultrastructural level where an intricate circuitry is evident (Fig. 1.2). A variety of neuronal subtypes partakes in this and can be classed in terms of functional and structural characteristics. Subclasses include sensory and motor, excitatory, and inhibitory. There are other neuronal subtypes and neurotransmitters present within the ENS (Table 1.1) akin to and aligned with those present in the CNS befitting the title conferred upon the ENS as the “second brain.”

Thedevelopment of the ENS is similarly complex (Chap. 2). The neurons and glia of the ENS all arise from precursor cells derived from the vagal, sacral, and rostral trunk neural crest [5, 6]. These cells migrate into the oral and anal ends of the embryo and enter the foregut and hindgut [7], colonizing the entire gastrointestinal tract. ENS maturity results from an adequate number of correctly differentiated neurons with sufficient axon outgrowth and branching. Several lines of evidence show that enteric neuronal development is not completed at birth. Indeed, in the murine gut, changes in morphology of the plexuses [8] and in the total number of neurons have been reported between the first 4 weeks of life [9]. Submucosal plexuses appear later than myenteric plexuses, and the number of submucosal neurons also increases during the same time period [10]. New post-mitotic neurons continue to appear until 3 weeks of postnatal life in the rat gut [11]. Although the pan neuronal marker PGP9.5 is present very early in the embryonic gut (E10.5 in the mouse) [12, 13], neurochemical phenotypic differentiation occurs later during embryonic development and even in postnatal life for cholinergic and peptidergic neurons [14, 15]. ENS neurochemical maturation reaches an adult pattern only at 1 month of postnatal life. In infants, data on functional maturation of the ENS are lacking but it has been reported that the number of cell bodies present within ganglia appears to change according to the age of the individual between 1 day of age and 15 years [16].