Hydras, without a central nervous system, seem to have a sleep-like state; seems a conserved sleep mechanisms during the evolutionary development of the central nervous system

A sleep-like state in Hydra unravels conserved sleep mechanisms during the evolutionary development of the central nervous system. Hiroyuki J. Kanaya et al. Science Advances Oct 7 2020:Vol. 6, no. 41, eabb9415. DOI: 10.1126/sciadv.abb9415

Abstract: Sleep behaviors are observed even in nematodes and arthropods, yet little is known about how sleep-regulatory mechanisms have emerged during evolution. Here, we report a sleep-like state in the cnidarian Hydra vulgaris with a primitive nervous organization. Hydra sleep was shaped by homeostasis and necessary for cell proliferation, but it lacked free-running circadian rhythms. Instead, we detected 4-hour rhythms that might be generated by ultradian oscillators underlying Hydra sleep. Microarray analysis in sleep-deprived Hydra revealed sleep-dependent expression of 212 genes, including cGMP-dependent protein kinase 1 (PRKG1) and ornithine aminotransferase. Sleep-promoting effects of melatonin, GABA, and PRKG1 were conserved in Hydra. However, arousing dopamine unexpectedly induced Hydra sleep. Opposing effects of ornithine metabolism on sleep were also evident between Hydra and Drosophila, suggesting the evolutionary switch of their sleep-regulatory functions. Thus, sleep-relevant physiology and sleep-regulatory components may have already been acquired at molecular levels in a brain-less metazoan phylum and reprogrammed accordingly.

DISCUSSION

Our demonstration of the sleep-like state in Hydra and the commonality of sleep-regulatory genes, neurotransmitters, and physiology provide important insights into how ancestral sleep has evolved with developing CNS and how sleep-regulatory pathways have been reorganized accordingly. While the two-process model for shaping daily sleep has been widely accepted (12), free-running circadian rhythms are not readily detectable in Hydra behaviors. This observation contrasts with circadian control of the quiescence state in the cnidarian jellyfish (5). Circadian clocks are not an essential prerequisite for sleep behaviors because animal species with no overt circadian rhythms (e.g., Caenorhabditis elegans) or circadian clock mutants in Drosophila and mammals exhibit sleep. Circadian rhythms have also been observed widely in nonanimal kingdoms, where sleep-like states are not recognized. Nonetheless, our discovery of 4-hour free-running rhythms in Hydrasleep may reflect an evolutionary intermediate for circadian clock-dependent sleep given that circadian rhythms emerge from coupled ultradian oscillators (33). We also reason that the ultradian rhythms in Hydra sleep could be an ancestral form of the sleep-stage cycling in mammals. In this sense, Hydra may represent one of the most primitive animal models for sleep.

Dopamine is a wake-promoting molecule conserved across animal species (1). We, however, showed that dopamine promotes Hydra sleep. This unexpected finding suggests that dopamine’s sleep-regulatory function may depend on how dopaminergic circuits are incorporated into sleep-regulatory pathways of the developing CNS. Consistent with this idea, dopamine is one of the major arousal neurotransmitters in adult flies, whereas it is dispensable for sleep in developing larvae (31). We speculate that the functional flipping of specific sleep-regulatory pathways (e.g., dopamine and ornithine) may have occurred during the evolutionary development of CNS. On the other hand, sleep-promoting pathways involving melatonin, GABA, or PRKG1 may have persisted in this process.

Our evidence does not necessarily exclude the possible contribution of the diffuse nerve net to Hydra sleep. Emerging evidence, however, indicates the presence of sleep-wake cycles of cell-autonomous nature and sleep-regulatory mechanisms of non-neuronal origin in mammals and Drosophila (1). Likewise, dopamine may contribute to Hydra sleep via its indirect effects on peripheral tissues (e.g., metabolism, cell growth, and oxidative stress) (34). We predict that essential metabolism (e.g., ornithine-derived metabolic pathways) would play a key role in shaping these ancestral forms of sleep, and Hydra would act as an important node in the phylogenetic tree of sleep for validating this hypothesis. Future studies should further mine phylogenetic nodes to illustrate the evolutionary trace of sleep-regulatory mechanisms at high resolution and elucidate the origin of sleep.