Miniature endoscope for high resolution electrophysiological recordings from the colon of live mice

A major weakness in the field of neurogastroenterology research has been a lack of technology to determine the spatial and temporal coordination of electrical activity along the gastrointestinal (GI) tract in-vivo, without requiring a surgical procedure. To overcome this weakness, we developed a miniaturized endoscope consisting of 128 iridium oxide recording sensors that allowed us to make high resolution intraluminal electrophysiological recordings in-vivo from the mucosal surface of the terminal large intestine of anesthetized mice. Recordings revealed discharges of smooth muscle action potentials organized into complex spatiotemporal patterns. The patterns were modified by pharmacological agents donepezil and atropine that stimulated or suppressed cholinergic neurotransmission, respectively. The patterns were also ablated by benzalkonium chloride, known to disrupt the function of the enteric nervous system. The endoscope was further validated under ex-vivo recording conditions, where blocking enteric neural activity with tetrodotoxin (TTX) again altered spontaneously occurring action potential patterns. This approach offers a unique opportunity to easily characterize normal and dysfunctional patterns of GI electrical activity in genetically modified and/or diseased mouse models, including drug discovery and high-throughput studies.