Do worms sing lullabies to go to sleep?

A look into worms’ neural sleep mechanisms

Photo by Fabian Oelkers on Unsplash

While the need for food and reproduction appears logical, evolution has left us with an enigma when it comes to sleep. Countless articles describe the importance of sleep in humans and depending on the context of your search you might face yourself with different interpretations. A chemist might examine chemicals required to induce sleep, an immunologist the fascinating involvement of your immune system during sleep. A neuroscientist might discuss the different stages of sleep whereas a psychiatrist might consider how insomnia and other sleep disorders affect your health and productivity. Despite their distinct expertise, they would all likely agree on two points: that sleep is an essential function and that we understand very little about sleep. Though researchers have categorized many disorders related to lack of adequate sleep, not long ago they had no idea why we needed sleep in the first place. Additionally, the details of how our brains switch from one sleep stage to another and other complex sleep processes remain a mystery. In their 2017 paper, Annika et al. examine these mechanisms in a more accessible nervous system- that of the roundworm Caenorhabditis elegans.

You might be wondering, how can a worm’s nervous system in any form compare to the remarkable work of evolution that is the human brain? Although it might come as a surprise, some of the behavioural states the mammalian brain goes through during sleep have been identified in many other organisms. This list, ranging anywhere from fish to insects, suggests that some aspects of sleep might be universal across all nervous systems. In their paper, Annika et al. establish C. Elegans as their model to study state transitions during sleep. The simplicity of the worm’s nervous system, composed of only 302 neurons, allows the authors to examine individual neurons during different brain states.

The authors describe two general states for the worms. The worms can either be in a more active state called non-lethargic or in a drowsy sleep-like state called lethargic. To induce state shifts, the scientists use previous findings of how roundworms respond to different pressures of oxygen.

Just like for any other animal, their environment provides key cues for behaviour. We will first consider lethargic worms. When a 10% oxygen concentration is sensed by the lethargic worms, they shift into a low activity dormant state called quiescence. In contrast, increasing the oxygen concentration to 21% for a given time induces arousal and a switch to the awake state. When the oxygen is then dropped back to 10%, the lethargic worms go back into dormancy.

During this sleep-like state, roundworms become immotile and have decreased responses to environmental stimuli. Annika et al. provide here an excellent use of state-of-the-art calcium imaging techniques to monitor the worm brains. Because neurons use calcium to fire, tracing calcium using indicators provides the scientist with a detailed overview of brain activity. Using this method, the scientists observed reduced activity in both the sensory and motor areas of the worm brain- which justifies the worms’ behaviour. The authors also observed significantly elevated activation of two modulatory neurons (RIS) during this dormancy state. The authors explain that the two RIS neurons were, by themselves, sufficient to induce this sleep-like immobility in worms when activated directly by the scientists. Overall, the authors report that the neuronal activity during this period of dormancy in worms resembles brain wave activity studied in mammalian sleep.

The two different oxygen conditions are not arbitrary, but rather approximate a worm’s natural environment. For example, when worms aggregate with one another, they form an area of low oxygen concentration. The authors make an excellent point, proposing that the reduced response to stimuli in low oxygen environments signifies that the worm is in a safe environment. In contrast to lethargic worms, these behaviour changes in response to oxygen do not apply to non-lethargic worms. Most non-lethargic worms do not respond to these stimuli and remain active even in low oxygen concentrations.

These findings lead to the logical questioning of how worms sense oxygen concentrations in the first place. According to Annika et al., the detection of oxygen is part of an arousal maintaining circuit and that a neuropeptide receptor (NPR-1) plays a crucial role in modulating this awakening. To understand the role of NPR-1, the authors examine the difference in response to oxygen concentrations between lethargic worms expressing different NPR-1 genes. They show that reduced NPR-1 activity correlates to a decreased sensory neuron activation during the dormant state in worms. This finding suggests that NPR-1 serves as a threshold setter for arousal in lethargic worms. The authors propose that during the lethargic state, roundworms’ brain is in quiescence by default and that it is the presence of stimuli, i.e. 21% oxygen, that causes the network to deviate into arousal. In contrast, they suggest that for non-lethargic worms, their brain’s default state is maintaining activity despite environmental stimuli. This hypothesis explains why non-lethargic worms react differently compared to lethargic ones.

Why is this of any importance?

Sleep touches many domains and affects our daily productivity and overall health. Health experts suggest that sleep is an essential process for learning, memory as well as growth. To a neuroscientist like myself, this study provides interesting and detailed findings while reminding us of the importance of studying animal models. Annika et al. provide us with neuroimaging techniques to study network mechanisms and evolution itself. The paper provides clear evidence of evolutionarily preserved processes and highlights findings that can be used to expand our understanding of sleep and health. Crucially, it brings up an important point of how complex processes, such as immobility during sleep, could be controlled merely by two modulatory neurons. This probes into our understanding of hierarchical processing in the brain and makes us wonder how much conscious control we really have over our own bodies. Therefore, while studying these simple organisms might not reveal exactly how to heal chronic sleep disorders, these studies provide us with the fundamental knowledge to answer more complex questions.