Epidermal Growth Factor Signaling Promotes Sleep through a Combined Series and Parallel Neural Circuit

Sleep requires sleep-active neurons that depolarize to inhibit wake circuits. Sleep-active neurons are under the control of homeostatic 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 stages and conditions in C. elegans, sleep requires a sleep-active neuron called RIS. Here, we defined the transcriptome of RIS and discovered that genes of the epidermal growth factor receptor (EGFR) signaling pathway are expressed in RIS. Because of cellular stress, EGFR directly activates RIS. 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 drowsiness neuron with two separable functions: (1) it inhibits specific behaviors, such as feeding, independently of RIS, (2) and it activates RIS. Whereas ALA plays a strong role in surviving cellular stress, surprisingly, RIS does not. In summary, EGFR signaling can depolarize RIS by an indirect mechanism through activation of the ALA neuron that acts upstream of the sleep-active RIS neuron and through a direct mechanism using EGFR signaling in RIS. ALA-dependent drowsiness, rather than RIS-dependent sleep bouts, appears to be important for increasing survival after cellular stress, suggesting that different types of behavioral inhibition play different roles in restoring health.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI0ZmY3N2NiMWEwMTdlMzljMjI3MDIxN2YyOWYxYmRiOSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc3OTcxODc0fQ.ey-9738T3LC4_2OEVVaa0qCtG5OthutCJZEP8q8GLprLT4o8g9O7V_PHITBLRyIinXHgqNRSPbYPc1vEj1jNIa_EC3MbTcA8_y_vOTCbE3ADLshhriMlpbkux7CI2tVxzVunMUVBQur56f0XZlTboQPf_lVXTR_IfOvRAtAsIBBGA6b0VoCNH98sG2IrnkAPktxoSFfVE9TwdpLC9bu9QOJmjd7N0Hkq4ZLlzXpcczZf6Z_w5RCTXvrqIFtGphXqQjzJv4Onyo_HIcVxtCv3hesMqut1Uoi0j9h1SxTvTuTy7NVdc05S89oqhITxJaHF0fxWr7PkKNxufaAOUp8KvA(mp4, (44.66 MB) Download video