896A Poster - 14. Neural circuits and behavior
Thursday April 07, 2:00 PM - 4:00 PM

Authors:
Elizabeth Knapp ¹; Henrike Scholz ²; Jeffrey Donlea ³; David Krantz ¹

Affiliations:
1) University of California, Los Angeles, Psychiatry, Los Angeles, CA; 2) University of Cologne, Animal Physiology, Köln, Germany; 3) University of California, Los Angeles, Neurobiology, Los Angeles, CA

Keywords:
h. circadian rhythms and sleep; g. neurotransmitters

Sleep is a critical process essential for life and is evolutionarily conserved from insects to mammals. Although sleep disruption has been linked to a variety of neurological and psychiatric disorders, the cellular mechanisms and neural circuitry involved in sleep regulation are not well understood. The biogenic amine serotonin (5-hydroxytryptamine, 5-HT) functions as a key neuromodulator of sleep behavior in both Drosophila and mammals. The relationship between serotonergic signaling and sleep has been studied for several decades, however its complex role in sleep regulation remains uncertain, with many studies showing it to play a role in both wakefulness and conversely sleep propensity. These complexities are further compounded by the fact that many antidepressants and antianxiety medications that work through selective inhibition of serotonin reuptake (SSRIs) have been shown to produce contradicting and various effects on sleep, ranging from insomnia to daytime somnolence.
In both Drosophila and mammals reuptake of serotonin from the synaptic cleft is mediated via the serotonin transporter (SERT). The relationships between sleep, neurological disorders, and SSRI medications strongly suggest that variations in extracellular serotonin levels as a result of increased or decreased SERT activity could play a key role in modulating sleep behaviors. The molecular mechanisms underlying this process, however, are not well understood in either humans or model systems.
In this study, we use Drosophila as a model system to study the mechanisms by which altering Drosophila SERT (dSERT) activity impacts sleep behavior. Here we use novel dSERT mutants to demonstrate that dSERT is required for regulating both proper sleep amount and architecture. In addition, we discovered the increased sleep drive exhibited in these dSERT mutants is differentially impacted by certain circadian and environmental factors. Lastly, our data suggests that distinct serotonergic circuits modulate daytime and nighttime sleep behaviors independently. Overall, our work provides new insight into the molecular mechanisms of neuromodulation in the context of sleep and enhances our understanding of how serotonergic signaling is involved in sleep behavior.