Optogenetic activation of the gut-brain axis in freely moving mice using a fully implantable wireless battery-free device.

Considerable evidence suggests that the gut-brain axis can influence behavior. However, there has been a conspicuous lack of technology to provide targeted wireless activation of the gut-brain axis in conscious freely moving animals. We utilized a miniature fully implantable battery-free device to apply highly controlled optogenetic stimuli to the terminal region of gastrointestinal tract, in conscious freely moving mice. The optical stimulator was implanted and secured on the serosal surface of the distal colon and rectum to characterize the behavioral responses evoked by optogenetic stimulation of axons expressing channelrhodopsin (ChR2) driven by the Trpv1 promoter (Trpv1^Cre+ChR2 mice). In freely moving Trpv1^Cre+ChR2 mice, trains of blue light pulses to the distal colon and rectum induced increased abdominal grooming and reduced movement. In contrast to stimulation of the gut, trains of stimuli applied to the peritoneal cavity evoked writhing and abdominal contraction. Anterograde labeling from nodose ganglia revealed sparse vagal afferent axons and endings in the proximal and mid colon, with no labeled axons caudal of the mid colon (within 30 mm of the anus). The distal colon and rectum were densely innervated by spinal afferents. The findings demonstrate that wireless optogenetic stimulation of the gut-brain axis can induce specific behavioral patterns in conscious freely moving rodents, using fully implantable battery-free technology.NEW & NOTEWORTHY The findings demonstrate that distinct behavioral changes can be induced by wireless activation of the terminal region of the large intestine (distal colon and rectum) in freely moving rodents, using fully implantable battery-free devices.