1534-P: The Role of Differentially Located Mouse Intrapancreatic Neurons in Islet ß-Cell and Acinar Cell Function

In the mouse, cholinergic neurons within the pancreas are organized in ganglia that can be classified based on their location: acinar ganglia embedded in the exocrine compartments versus neuroinsular ganglia located adjacent to endocrine islets. Although they form a network within the organ, it is unclear if this anatomical segregation allows channeling external input (e.g. efferent vagal input) to the pancreas in a labeled-line manner, thus differentially affecting exocrine and endocrine function. Our study aims to test the hypothesis that pancreatic innervation can be segregated into (1) acinar ganglia that preferentially target exocrine tissues controlling digestive enzyme secretion and (2) neuroinsular ganglia that preferentially target glucoregulatory endocrine islets. To test this hypothesis, we used the chemogenetic approach to stimulate cholinergic neurons in living pancreas slices from mice expressing DREADD receptors under the control of the choline acetyltransferase promoter (ChAT-hM3Dq DREADD mice). Our results showed that only cholinergic neurons express DREADD receptors and respond to CNO stimulation with a characteristic muscarinic response. We were able to measure Ca2+ responses in different tissue compartments. Acinar cells have a stronger Ca2+ response when compared with islet cells after neuronal stimulation. Ca2+ responses in the beta cell population were sparse, localized, and only at higher glucose concentrations. Acinar and islet beta cell activation were confirmed by increases in amylase and insulin secretion after neuronal stimulation from dynamic perfusion experiments. These preliminary results showed that the chemogenetic approach to target cholinergic neurons in living pancreas slices is a powerful platform for studying the effects of local neural activation on different cell populations providing the basis for future neuromodulation experiments.