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<h5 class="section-title" id="d8542552e212">Background & Aims</h5>
<p id="P4">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.
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<h5 class="section-title" id="d8542552e217">Methods</h5>
<p id="P5">We generated transgenic mice with Cre-mediated expression of light-sensitive
channelrhodopsin-2
(CHR2) in calretinin neurons (CAL-ChR2
<i>Cre+</i> mice);
<i>Cre−</i> 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
<i>in vitro</i> and by fecal output
<i>in vivo</i>.
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<h5 class="section-title" id="d8542552e234">Results</h5>
<p id="P6">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
<i>in vitro</i> (75 ± 17% vs 32 ± 8% for controls) (
<i>P</i> <.05).
<i>In vivo</i>, activation of wireless light-emitting diodes implanted onto the colon
wall significantly
increased hourly fecal pellet output in conscious, freely moving mice (4.17 ± 0.4
vs 1.3 ± 0.3 in controls) (
<i>P</i><.001).
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<h5 class="section-title" id="d8542552e251">Conclusions</h5>
<p id="P7">In studies of mice, we found that focal activation of a subset of enteric
neurons
can increase motility of the entire colon
<i>in vitro</i>, and fecal output
<i>in vivo</i>. Optogenetic control of enteric neurons might therefore be used to
modify gut motility.
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