Implantable Bioelectronics for Gut Electrophysiology

Abstract

The gastrointestinal tract is regulated by a complex network of electrically-active cell types that communicate to drive gut function. One of these systems, the enteric nervous system, represents a primary point of contact for a host of factors that influence bodily health and behavior. This division of the autonomic nervous system is unique in both its extensivity, with neurons distributed throughout the gastrointestinal tract from the esophagus to the rectum, and its capability for local information processing. However, the constant intrinsic and extrinsic motion of the gut as well as the sparse distribution of the neurons that constitute the enteric nervous system has made, access and analysis for study of this important component of the gastrointestinal tract exceedingly challenging. Here, we present the construction and validation of a bioelectronic implant for accessing neural information from the distal colon. The implant, constructed for compatibility with a novel surgical approach applicable across multiple species, is designed to be positioned within the colonic wall in close proximity to the enteric nervous plexi. We captured complex multi-frequency electrophysiological responses to neural chemical stimulants and showed that we can record distension activity mimicking gut motility. We also show the feasibility of utilizing this device for recording from putative single neurons in freely-moving rats and examining colonic activity in the context of food intake and stress. This work marks a significant advancement in understanding the complex pathways of the gut-brain axis. Our bioelectronic monitoring system demonstrates the power of real-time electrophysiological monitoring for the distal areas of the autonomic nervous system. Furthermore, direct access to the communication pathways of the enteric nervous system paves the way for novel neuromodulation strategies targeting the gut-brain axis.