AUTHOR=Seugnet Laurent , Dissel Stephane , Thimgan Matthew , Cao Lijuan , Shaw Paul J. 

TITLE=Identification of Genes that Maintain Behavioral and Structural Plasticity during Sleep Loss

JOURNAL=Frontiers in Neural Circuits

VOLUME=11

YEAR=2017

URL=https://www.frontiersin.org/journals/neural-circuits/articles/10.3389/fncir.2017.00079

DOI=10.3389/fncir.2017.00079

ISSN=1662-5110

ABSTRACT=<p>Although patients with primary insomnia experience sleep disruption, they are able to maintain normal performance on a variety of cognitive tasks. This observation suggests that insomnia may be a condition where predisposing factors simultaneously increase the risk for insomnia and also mitigate against the deleterious consequences of waking. To gain insight into processes that might regulate sleep and buffer neuronal circuits during sleep loss, we manipulated three genes, <italic>fat facet</italic> (<italic>faf)</italic>, <italic>highwire</italic> (<italic>hiw</italic>) and the GABA receptor <italic>Resistance to dieldrin</italic> (<italic>Rdl</italic>), that were differentially modulated in a <italic>Drosophila</italic> model of insomnia. Our results indicate that increasing <italic>faf</italic> and decreasing <italic>hiw</italic> or <italic>Rdl</italic> within wake-promoting large ventral lateral clock neurons (lLNvs) induces sleep loss. As expected, sleep loss induced by decreasing <italic>hiw</italic> in the lLNvs results in deficits in short-term memory and increases of synaptic growth. However, sleep loss induced by knocking down <italic>Rdl</italic> in the lLNvs protects flies from sleep-loss induced deficits in short-term memory and increases in synaptic markers. Surprisingly, decreasing <italic>hiw</italic> and <italic>Rdl</italic> within the Mushroom Bodies (MBs) protects against the negative effects of sleep deprivation (SD) as indicated by the absence of a subsequent homeostatic response, or deficits in short-term memory. Together these results indicate that specific genes are able to disrupt sleep and protect against the negative consequences of waking in a circuit dependent manner.</p>