Optical Imaging of Pancreatic Innervation

Abstract

At the time of Ivan Pavlov, pancreatic innervation was studied by looking at pancreas secretions in response to electrical stimulation of nerves. Nowadays we have ways to visualize neuronal activity in real time thanks to advances in fluorescent reporters and imaging techniques. We also have very precise optogenetic and pharmacogenetic approaches that allow neuronal manipulations in a very specific manner. These technological advances have been extensively employed for studying the central nervous system and are just beginning to be incorporated for studying visceral innervation. Pancreatic innervation is complex, and the role it plays in physiology and pathophysiology of the organ is still not fully understood. In this review we highlight anatomical aspects of pancreatic innervation, techniques for pancreatic neuronal labeling, and approaches for imaging pancreatic innervation in vitro and in vivo.

Schwann Cells in Digestive System Disorders

“…Advanced optical clearing and imaging techniques, similar to the ones used in the pancreas [ 119 , 120 ] and the liver [ 190 ], are extremely useful. However, depending on the assay or marker used, large discrepancies can be observed [ 120 ], perhaps due to sample preparation, the minute size of the axons, and the low quantities of the target protein [ 118 ]. In addition, the source of glial cells in these organs and various conditions remains elusive.…”

“…The pancreas is innervated by extrinsic and intrinsic neurons. Extrinsic are mainly associated with the vagus nerve and sympathetic splanchnic nerves, as well as sensory innervation, while intrinsic stem from intrapancreatic ganglia [ 4 , 117 , 118 ]. In addition, there are connections to the ENS [ 4 ].…”

“…In addition, there are connections to the ENS [ 4 ]. Nerve endings can synapse at the ganglia or directly contact other pancreatic structures, for example, blood vessels, ducts, acini, and islets [ 118 ].…”

“…Recently, several studies have addressed pancreatic innervation in more detail using advanced tissue-clearing and imaging techniques [ 118 , 119 , 120 , 121 ]. Quantitative imaging of the adult mouse pancreas revealed that the nerve distribution in the organ is not uniform, with a larger volume of nerve seen closer to the duodenum.…”

“…Together, these studies demonstrate a complex context-dependant paracrine function of SCs in the stroma of pancreatic tumours and warrant further exploration, for example, to establish whether the dispersed SCs found in the tumour stroma are associated with the axons or are independent and which exact nerves contribute SCs to the tumour microenvironment. A more thorough investigation, involving 3D imaging of normal and tumour sites in mouse and human tissue, similar to that performed in the endocrine pancreas, might answer these questions [ 118 , 119 ]. Importantly, SC involvement is apparent already in early pre-cancerous lesions and present an opportunity for potential intervention [ 51 , 74 , 75 ].…”