Central control of gastrointestinal functions in health and disease

Thanks to its extensive intrinsic (enteric) neural networks spanning its entire length, the gastrointestinal (GI) tract has long been recognized for its ability to operate independently of the central nervous system (CNS). Despite that, the CNS provides both sympathetic and parasympathetic inputs to the GI tract, which confers an additional layer of regulation, modulation, and integration over GI functions. The sympathetic nervous system provides neurovascular control of GI blood flow in addition to its effects to decrease mucosal secretion, regulate sphincter tone, and modulate motility, principally via prejunctional and presynaptic actions. The parasympathetic nervous system, however, exerts both excitatory and inhibitory effects; the extent to which this influences gut functions varies throughout the length of the GI tract. Recent studies have also demonstrated that, in addition to regulation via the autonomic nervous system, "higher" CNS nuclei also provide a significant degree of influence over GI functions under both physiological and pathophysiological conditions. In addition to describing the anatomical neurocircuits and physiological functions of the extrinsic inputs to the GI tract, this review also discusses the roles of brain stem, midbrain, and cortical nuclei that influence the gut within the context of relevant physiological and pathophysiological conditions.