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bioRxiv · 10.1101/2024.10.02.616374

A heteromeric nicotinic acetylcholine receptor promotes sleep by relaying GABAergic signals within a locus of motor and sensory integration

Yumita, T.·Ahamed, H.·Hatch, H. A.·Cossentino, I.·Louka, C.·Stavropoulos, N.
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Abstract

Locomotor inactivity and reduced sensory responsiveness are defining attributes of sleep, yet the underlying mechanisms are not well understood. In particular, the molecular and circuit mechanisms by which sleep-regulatory signals from the brain restrict movement and sensation remain largely ill-defined. Here we identify a nicotinic acetylcholine receptor (nAChR) that promotes sleep in Drosophila through its expression in GABAergic neurons of the ventral nerve cord (VNC), a center for motor and sensory systems. Biochemical, genetic, and pharmacological manipulations indicate that a heteromeric nAChR containing the 1 and {beta}1 subunits promotes sleep by coupling cholinergic input to GABA release in the VNC and the likely inhibition of motor neurons, sensory afferents, or both. The functional parallels of the VNC and the mammalian spinal cord suggest that disruptions of analogous inhibitory circuits in humans may impair suppression of behavioral activity and sensory inputs during sleep and contribute to sleep disorders.

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Yumita, T., Ahamed, H., Hatch, H. A., Cossentino, I., Louka, C., Stavropoulos, N.. 2024-10-03. A heteromeric nicotinic acetylcholine receptor promotes sleep by relaying GABAergic signals within a locus of motor and sensory integration. https://doi.org/10.1101/2024.10.02.616374

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