A GABAergic and peptidergic sleep neuron as a locomotion stop neuron with compartmentalized Ca2+dynamics.

Animals must slow or halt locomotion to integrate sensory inputs or to change direction. In Caenorhabditis elegans, the GABAergic and peptidergic neuron RIS mediates developmentally timed quiescence. Here, we show RIS functions additionally as a locomotion stop neuron. RIS optogenetic stimulation caused acute and persistent inhibition of locomotion and pharyngeal pumping, phenotypes requiring FLP-11 neuropeptides and GABA. RIS photoactivation allows the animal to maintain its body posture by sustaining muscle tone, yet inactivating motor neuron oscillatory activity. During locomotion, RIS axonal Ca2+ signals revealed functional compartmentalization: Activity in the nerve ring process correlated with locomotion stop, while activity in a branch correlated with induced reversals. GABA was required to induce, and FLP-11 neuropeptides were required to sustain locomotion stop. RIS attenuates neuronal activity and inhibits movement, possibly enabling sensory integration and decision making, and exemplifies dual use of one cell across development in a compact nervous system

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