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bioRxiv · 10.1101/656512

Epidermal Growth Factor signaling acts directly and through a sedation neuron to depolarizes a sleep-active neuron following cellular stress

Konietzka, J.·Fritz, M.·Spiri, S.·McWhirter, R.·Leha, A.·Palumbos, S.·Steuer Costa, W.·Oranth, A.·Gottschalk, A.·Miller, D.·Hajnal, A.·Bringmann, H.
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Abstract

Sleep is induced by sleep-active neurons that depolarize at sleep onset to inhibit wake circuits. Sleep-active neurons are under the control of homeostatic and allostatic mechanisms that determine sleep need. However, little is known about the molecular and circuit mechanisms that translate sleep need into the depolarization of sleep-active neurons. During many conditions in C. elegans sleep induction requires a sleep-active neuron called RIS. Here, we defined the transcriptome of RIS to discover that genes of the Epidermal Growth Factor Receptor (EGFR) signaling pathway are expressed in RIS. With cellular stress, EGFR activates RIS, and RIS induces sleep. Activation of EGFR signaling in the ALA neuron has previously been suggested to promote sleep independently of RIS. Unexpectedly, we found that ALA activation promotes RIS depolarization. Our results suggest that ALA is a sedating neuron with two separable functions. (1) It inhibits specific wakefulness behaviors independently of RIS, (2) and it activates RIS to induce sleep. Whereas ALA plays a strong role in surviving cellular stress, surprisingly, RIS does not. In summary, EGFR signaling can induce sleep-active neuron depolarization by an indirect mechanism through activation of the sedating ALA neuron that acts upstream of the sleep-active RIS neuron as well as through a direct mechanism using EGFR signaling in RIS. Sedation rather than sleep appears to be important for increasing survival following cellular stress, suggesting that sedation and sleep play different roles in restoring health.\n\nHighlights- The transcriptome of the sleep-active RIS neuron reveals the presence of the EGFR signaling machinery\n- EGFR activates RIS directly upon cellular stress to induce sleep bouts\n- In parallel, EGFR activates RIS indirectly through the sedating ALA neuron\n- Sedation rather than sleep bouts support survival following cellular stress

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Konietzka, J., Fritz, M., Spiri, S., McWhirter, R., Leha, A., Palumbos, S., Steuer Costa, W., Oranth, A., Gottschalk, A., Miller, D., Hajnal, A., Bringmann, H.. 2019-06-03. Epidermal Growth Factor signaling acts directly and through a sedation neuron to depolarizes a sleep-active neuron following cellular stress. https://doi.org/10.1101/656512

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