Sensory Innervation of the Pancreatic Islet

Sensory innervation of viscera is an important component for proper maintenance of body homeostasis. Visceral stimuli are detected by free nerve endings of the vagus nerve and are transmitted to the hindbrain via sensory neurons. However, the signals that activate vagal sensory neurons in the periphery are not known. The objective of this study is to identify and characterize the population of vagal sensory neurons that innervates the pancreas. Using immunohistochemistry for sensory neuronal marker substance P, we show that sensory innervation targets islet periphery. Upon islet damage (in NOD model or following streptozotocin (STZ) treatment), density of islet sensory innervation increases. Expression of the immediate early gene c-Fos, shows that hindbrain neurons in the nucleus of the solitary tract (NTS) respond to severe islet inflammation induced by STZ. We assessed response profile of pancreatic sensory neurons using in-vivo calcium imaging of mouse vagal sensory ganglion (nodose). This method allows us to monitor in real time the response profile of sensory neurons and identify pancreas-specific subpopulations by chemical stimulation of the exteriorized pancreas. We have identified sensory neurons that respond to pancreatic application of serotonin (5HT) and cholecystokinin (CCK). The observed response profile suggests that these neuronal populations are tuned to sense differentially endocrine and exocrine pancreas. While endocrine sensory neurons are sensing local 5HT that is co-released with insulin, exocrine neurons sense CCK a hormone that stimulates release of digestive enzymes. Altogether our data suggest that pancreatic sensory neurons could be important regulators of pancreatic physiology. By taking a snapshot of endocrine and exocrine pancreatic microenvironments and sending this information to the brain, sensory neurons might trigger feedback loops and help the organ to be tuned to physiological needs. Disclosure M. Makhmutova: None. J. Weitz: None. R. Rodriguez Diaz: None. J. Almaca: None. E. Bernal-Mizrachi: None. A. Caicedo: None.