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Gastroenterology. 2018 Aug;155(2):514-528.e6. doi: 10.1053/j.gastro.2018.05.029. Epub 2018 May 18.

Optogenetic Induction of Colonic Motility in Mice.

Author information

1
College of Medicine and Public Health and Centre for Neuroscience, Flinders University, Adelaide, Australia.
2
Department of Anesthesiology, The Center for the Study of Itch, Washington University School of Medicine, St Louis, Missouri.
3
Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri.
4
SA Biomedical Engineering, SA Health, Government of South Australia, Adelaide, Australia.
5
Department of Anesthesiology, The Center for the Study of Itch, Washington University School of Medicine, St Louis, Missouri. Electronic address: hongzhen.hu@wustl.edu.
6
College of Medicine and Public Health and Centre for Neuroscience, Flinders University, Adelaide, Australia. Electronic address: nicholas.spencer@flinders.edu.au.

Abstract

BACKGROUND & AIMS:

Strategies are needed to increase gastrointestinal transit without systemic pharmacologic agents. We investigated whether optogenetics, focal application of light to control enteric nervous system excitability, could be used to evoke propagating contractions and increase colonic transit in mice.

METHODS:

We generated transgenic mice with Cre-mediated expression of light-sensitive channelrhodopsin-2 (ChR2) in calretinin neurons (CAL-ChR2 Cre+ mice); Cre- littermates served as controls. Colonic myenteric neurons were analyzed by immunohistochemistry, patch-clamp, and calcium imaging studies. Motility was assessed by mechanical, electrophysiological, and video recording in vitro and by fecal output in vivo.

RESULTS:

In isolated colons, focal light stimulation of calretinin enteric neurons evoked classic polarized motor reflexes (50/58 stimulations), followed by premature anterograde propagating contractions (39/58 stimulations). Light stimulation could evoke motility from sites along the entire colon. These effects were prevented by neural blockade with tetrodotoxin (n = 2), and did not occur in control mice (n = 5). Light stimulation of proximal colon increased the proportion of natural fecal pellets expelled over 15 minutes in vitro (75% ± 17% vs 32% ± 8% for controls) (P < .05). In vivo, activation of wireless light-emitting diodes implanted onto the colon wall significantly increased hourly fecal pellet output in conscious, freely moving mice (4.2 ± 0.4 vs 1.3 ± 0.3 in controls) (P < .001).

CONCLUSIONS:

In studies of mice, we found that focal activation of a subset of enteric neurons can increase motility of the entire colon in vitro, and fecal output in vivo. Optogenetic control of enteric neurons might therefore be used to modify gut motility.

KEYWORDS:

Colonic Migrating Motor Complex; Gut Motility; Myoelectric Complex; Peristalsis

PMID:
29782847
DOI:
10.1053/j.gastro.2018.05.029
[Indexed for MEDLINE]

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