Aims
Recently, it was demonstrated that optogenetics could be used to stimulate enteric calretinin neurons, leading to increased colonic transit in vitro and in vivo. The aim of the current study was to determine if similar approaches could be used to stimulate the isolated mouse small intestine, with the aim of potentially also improving transit in the small bowel.
Background and aims
Recently, it was demonstrated that optogenetics could be used to stimulate enteric calretinin neurons, leading to increased colonic transit in vitro and in vivo. The aim of the current study was to determine if similar approaches could be used to stimulate the isolated mouse small intestine, with the aim of potentially also improving transit in the small bowel.
Conclusion
Focal illumination of the small intestine does not appear as effective at inducing propulsive motor activity as has been demonstrated in the colon of the same colony mice. This study suggests caution should be exercised when assuming optogenetic technology is equally effective at increasing GI transit in the small intestine as in the large intestine of mice.
Methods
Cre-Lox recombination was used to generate transgenic mice expressing the light-sensitive ion channel channelrhodopsin-2 (ChR2) in calretinin neurons.
Results
Spontaneous migrating motor complexes were recorded from isolated terminal small intestine in both CalCre+ mice expressing ChR2 in calretinin-expressing neurons and experimental controls, CalCre-. Trains of blue light pulses (20 ms, 5 Hz, 20s) evoked a brief local contraction of circular muscle, but never a premature MMC, irrespective of light intensity (1-40 mV/mm2) or the region of ileum stimulated. However, MMCs were readily evoked by calretinin neuron activation in colon, consistent with our previous study. Light-evoked contractions of the terminal small bowel were hexamethonium-resistant (300 μM), but blocked by tetrodotoxin (0.6 μM). Light-evoked smooth muscle contraction did not change the pacemaker frequency underlying MMCs.