Light-Dependent Regulation of Sleep and Wake States by Prokineticin 2 in Zebrafish

Abstract

Summary Light affects sleep/wake behaviors by providing an indirect cue that entrains circadian rhythms and also by inducing a direct and rapid regulation of behavior. While circadian entrainment by light is well characterized at the molecular level, mechanisms that underlie the direct effect of light on behavior are largely unknown. In zebrafish, a diurnal vertebrate, we found that both overexpression and mutation of the neuropeptide prokineticin 2 (Prok2) affect sleep/wake behaviors in a light-dependent but circadian-independent manner. In light, Prok2 overexpression increases sleep and induces expression of galanin (galn), a hypothalamic sleep-inducing peptide. We also found that light-dependent, Prok2-induced sedation requires prokineticin receptor 2 (prokr2) and is strongly suppressed in galn mutants. These results suggest that Prok2 antagonizes the direct wake-promoting effect of light in zebrafish, in part through the induction of galn expression in the hypothalamus.

Impacts of artificial light at night on sleep: A review and prospectus

“…Light at night can therefore disrupt circadian rhythms (Dominoni et al., ; Stevens & Zhu, ; Yadav, Verma, & Singh, ), which not only shifts the timing of the sleep–wake cycle, but also dampens its rhythm (Dijk & Archer, ; Fisher et al., ). Second, exposure to light can have direct effects on sleep and wakefulness, without necessarily affecting circadian rhythms (Altimus et al., ; Cajochen, Zeitzer, Czeisler, & Dijk, ; Chang, Scheer, Czeisler, & Aeschbach, ; Chen et al., ; Gandhi et al., ; Rattenborg, Obermeyer, Vacha, & Benca, ). Finally, light at night can allow animals that are normally diurnal to extend their activity into the night (e.g., Bakken & Bakken, ; Gaston et al., ; Santos et al., ; Stracey, Wynn, & Robinson, ; reviewed by Gaston et al., ).…”

The neuropeptide Galanin is required for homeostatic rebound sleep following increased neuronal activity

“…S4I). One potential regulator that should be examined in this context is the sleep-inducing neuropeptide Prokineticin2, which can upregulate galn transcription in zebrafish (Chen et al, 2017). The modest reduction of normal sleep at night in galn mutants under baseline conditions also points to other, as yet undiscovered, sleep regulators and hints that baseline and homeostatically-driven rebound sleep may have distinct modifying pathways.…”

“…The antisense c-fos riboprobe was transcribed from plasmid after subcloning a 716 bp PCR product generated using primers 5'-CCGATACACTGCAAGCTGAA-3' and 5'-ATTGCAGGGCTATGGAAGTG-3' (digestion with BamHI, transcribed with T7 RNA polymerase). The galn riboprobe has been previously described (Chen et al, 2017). Fluorescent ISH was essentially performed as above but probe detection was carried out with an anti-Dig-HRP antibody (1:1000 in 5% NGS).…”

Genetic sleep deprivation: using sleep mutants to study sleep functions

“…While one study could not find evidence for rapid eye movement during sleep, this result does not exclude the possibility that other components of REM sleep are present in zebrafish [80]. Major advantages of zebrafish as a sleep model are the high level of conservation of genes involved in sleep control, such as neuropeptide systems, a high level of conservation of key brain anatomical structures within a transparent brain, the possibility to model neuropsychiatric disorders as well as the possibility to scale up genetic and pharmacological screens [13,14,[81][82][83][84]. Several physical methods exist for SD in zebrafish.…”