Sensory Neurons that Detect Stretch and Nutrients in the Digestive System

Abstract

SUMMARY Neural inputs from internal organs are essential for normal autonomic function. The vagus nerve is a key body-brain connection that monitors the digestive, cardiovascular, and respiratory systems. Within the gastrointestinal tract, vagal sensory neurons detect gut hormones and organ distension. Here, we investigate the molecular diversity of vagal sensory neurons and their roles in sensing gastrointestinal inputs. Genetic approaches allowed targeted investigation of gut-to-brain afferents involved in homeostatic responses to ingested nutrients (GPR65 neurons) and mechanical distension of the stomach and intestine (GLP1R neurons). Optogenetics, in vivo ganglion imaging, and genetically guided anatomical mapping provide direct links between neuron identity, peripheral anatomy, central anatomy, conduction velocity, response properties in vitro and in vivo, and physiological function. These studies clarify the roles of vagal afferents in mediating particular gut hormone responses. Moreover, genetic control over gut-to-brain neurons provides a molecular framework for understanding neural control of gastrointestinal physiology.

Molecular and Functional Neuroscience in Immunity

“…Identifying selective patterns of afferent vagus nerve activity (neurograms) in response to different cytokines, including IL-1β and TNF, is an important first step toward addressing these questions (37). This line of research may further benefit from molecular tools recently used to perform genetic molecular profiling of vagal afferents with a role in pulmonary and gastrointestinal regulation (133, 134). Brain neuronal activation (c-Fos) following intestinal infection with C. jejuni has been detected in the NTS, the area postrema, the ventrolateral medulla, the LC, the thalamus, different hypothalamic nuclei, the amygdala, and the insular cortex (54).…”

Vasopressin and the Regulation of Thirst

“…Mice lacking acid-sensing taste receptors lost the ability to distinguish water from non-aqueous liquids such as oil. Esophageal and/or gastric sensors could also convey organ-specific information via the sensory vagus nerve [20], in a manner similar to the concept of appetite control suggested by Andermann and Lowell [21]. This involves feedforward control of hypothalamic activity via external cues regarding mealtimes, food, and water availability; this activity regulates feeding and water absorption to prevent future homeostatic perturbations.…”

The Effect of Microbiota and the Immune System on the Development and Organization of the Enteric Nervous System

“…In addition to its motor and secretory functions, the GI tract is the largest sensory organ of the body, which incessantly monitors the dynamic microenvironment of the gut wall and its lumen 6 . Several cellular systems contribute to the sensory function of the gut, including the enteroendocrine cells of the intestinal epithelium, the mucosal immune system, and the ENS 1 .…”

“…The integrated responses of these cellular networks enable the gut to build highly selective anatomic and functional barriers that allow absorption of useful nutrients and exclusion of harmful chemicals and micro-organisms. Information relating to the chemical composition and caloric value of ingested food, the dynamic equilibrium of the microbial ecosystem of the gut (microbiota), and the physiological state of the gut wall reaches the brain via the neurohumoral pathways of the microbiota–gut–brain (MGB) axis and allows the CNS to generate appropriate homeostatic and behavioral responses 6, 7, 8…”