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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.
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