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      Optogenetic Induction of Colonic Motility in Mice

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          Abstract

          <div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d8542552e212">Background &amp; 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. </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <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>. </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <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> &lt;.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>&lt;.001). </p> </div><div class="section"> <a class="named-anchor" id="S4"> <!-- named anchor --> </a> <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. </p> </div>

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          Author and article information

          Journal
          Gastroenterology
          Gastroenterology
          Elsevier BV
          00165085
          May 2018
          May 2018
          Article
          10.1053/j.gastro.2018.05.029
          6715392
          29782847
          c3fbf669-546d-4408-8487-e798aa6646e8
          © 2018

          http://www.elsevier.com/tdm/userlicense/1.0/

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