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      Alcohol Activates Scabrous-Notch to Influence Associated Memories

      , , , , ,
      Neuron
      Elsevier BV

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          Abstract

          <p id="P4">Drugs of abuse, like alcohol, modulate gene expression in reward circuits and consequently alter behavior. However, the <i>in vivo</i> cellular mechanisms through which alcohol induces lasting transcriptional changes are unclear. We show that <i>Drosophila</i> Notch/Su(H) signaling, and the secreted fibrinogen-related protein Scabrous, in mushroom body (MB) memory circuitry, is important for the enduring preference of cues associated with alcohol’s rewarding properties. Alcohol exposure affects Notch responsivity in the adult MB and alters Su(H) targeting at the <i>dopamine-2-like receptor (Dop2R).</i> Alcohol-cue training also caused lasting changes to the MB nuclear transcriptome, including changes in the alternative splicing of <i>Dop2R</i> and newly implicated transcripts like <i>Stat92E.</i> Together, our data suggest that alcohol-induced activation of the highly conserved Notch pathway and accompanying transcriptional responses in memory circuitry contribute to addiction. Ultimately this provides mechanistic insight into the etiology and pathophysiology of Alcohol Use Disorder. </p><p id="P5"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/d9e9e18c-b9c4-47c2-904b-97e77c93fec0/PubMedCentral/image/nihms-1510443-f0001.jpg"/> </div> </p>

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          Author and article information

          Journal
          Neuron
          Neuron
          Elsevier BV
          08966273
          December 2018
          December 2018
          : 100
          : 5
          : 1209-1223.e4
          Article
          10.1016/j.neuron.2018.10.005
          6323638
          30482693
          1329f288-2e22-4a94-a894-3355eb20ffd0
          © 2018

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

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