Tools for Controlling Activity of Neural Circuits Can Boost Gastrointestinal Research

Compelling evidence indicates that alterations of intestinal homeostasis, such as " leaky " epithelial barrier and changes in microbiota composition, can be associated with pathological adaptations of brain functions (Carabotti et al., 2015). On the other hand, just as disrupted gut homeostasis affects the brain, the brain can also exert a profound influence on the intestine as indicated by the elicitation of inflammatory bowel disease (IBD) or IBD-like conditions following stress and depression (for review see Di Giovangiulio et al., 2015). Recently, the recognition that microbiota influences signaling pathways regulating the central nervous system (CNS) has led to the concept of " microbiota–gut–brain axis " (Cryan and Dinan, 2012). Indeed, the routes of communication between brain and intestinal microbes rely on the immune system activation, and on the capability of microbiota to produce a number of neurochemicals (GABA, serotonin, dopamine) regulating learning, memory, and mood (Dinan et al., 2015; Moloney et al., 2015). With the evolving concept of psychoneuroimmunology the modalities by which the brain can influence intestinal functions and vice versa are becoming more evident, although mechanistically this bidirectional communication remains ill defined. For instance, patients with quiescent IBD show an increased probability of relapse when encountering chronic stress, adverse life events and depression (Mawdsley and Rampton, 2005). Similarly, the induction of an experimental depressive-like state induced by olfactory bulbectomy in mice caused reactivation of colitis (Ghia et al., 2009), suggesting that properly functioning central neuronal circuits are crucial for the maintenance of gut homeostasis. On the other hand, changes of gut microbiota composition can directly affect brain development in growing infants (Douglas-Escobar et al., 2013) and discrete perturbations of intestinal microflora were shown to induce behavioral abnormalities in mice (Desbonnet et al., 2015). Chronic intestinal inflammation observed in IBD patients is also associated with extra-intestinal symptoms including anxiety and depression-like behaviors (Graff et al., 2009) as well as gastrointestinal morbidities induced by alterations of the autonomic nervous system (ANS; Lindgren et al., 1993). Motility, secretion and vasoregulation are controlled by sympathetic and parasympathetic extrinsic branches, consisting of noradrenergic nerves dynamically interacting with immune cells and enteric neurons (located in the mucosa and the submucosa), and the vagus nerve broadly innervating the intestinal wall up to the myenteric plexus. An increase in brain cholinergic activity attenuates experimental colitis by the initiation of vagal anti-inflammatory pathways in the periphery (Ghia et al., 2006), whereas via their efferents to gut-associated lymphoid …