Sleep and Development in Genetically Tractable Model Organisms

Abstract

Sleep is widely recognized as essential, but without a clear singular function. Inadequate sleep impairs cognition, metabolism, immune function, and many other processes. Work in genetic model systems has greatly expanded our understanding of basic sleep neurobiology as well as introduced new concepts for why we sleep. Among these is an idea with its roots in human work nearly 50 years old: sleep in early life is crucial for normal brain maturation. Nearly all known species that sleep do so more while immature, and this increased sleep coincides with a period of exuberant synaptogenesis and massive neural circuit remodeling. Adequate sleep also appears critical for normal neurodevelopmental progression. This article describes recent findings regarding molecular and circuit mechanisms of sleep, with a focus on development and the insights garnered from models amenable to detailed genetic analyses.

Keywords: Caenorhabditis elegans; Danio rerio; Drosophila melanogaster; development; invertebrate sleep; ontogeny; sleep.

Figure 1

Postural/positional changes during sleep (right) and wakefulness (left) in model organisms. Worms assume a hockey-stick posture (Tramm et al. 2014). Flies have been observed to show a head “droop” and preference to sleep near food (Hendricks et al. 2000). Zebrafish exhibit two postures: floating with head droop or remaining horizontal near the bottom of the tank (Zhdanova et al. 2001).

Figure 2

Sleep ontogeny changes across phylogeny. Flies, fish, and worms all exhibit developmentally regulated changes to sleep amount/timing in a manner akin to that of humans. Fruit flies and zebrafish have increased sleep amount in early life compared to mature adults. Nematodes similarly exhibit developmental timing to sleep patterns.

Figure 3

The omnipresence of sleep may be a signature of its contribution to satisfying a constraint inherent to development. Should the time pressure of development be thought of as a universal constraint that can be mitigated by a sleep–wake cycle? All nervous systems originate from a single cell. In a restricted period of time, they must undergo structural plasticity (e.g., synaptogenesis) on a scale that is comparable to their full size. If sleep provides vital aspects of the solution to this challenge, its ubiquity in the animal kingdom may be related to the common feat of development (or neurodevelopment in particular). Much like the contributions of simple organisms to understanding developmental processes, facile genetics and tractable anatomy are key to understanding ontogenetic changes, core functions, and evolutionary origins of sleep.