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Research at Mass General
Hayley Mattison, PhD, is studying the neuronal circuits of tiny worms to learn more about the processes the brain uses to allow and maintain a state of sleep.
On a typical day, you will find me in the lab at my microscope taking images of neurons that ‘glow’ green in the brains of the microscopic worm, Caenorhabditis elegans (C. elegans).
As a postdoctoral fellow in the laboratory of Joshua Kaplan, PhD, in the Department of Molecular Biology at Massachusetts General Hospital, I study the neurons that control sleep in the worm. (Yes, worms sleep).
Worms have four larval stages between hatching and adulthood, and they undergo a sleep-like state called lethargus prior to entering each stage.
Sleep is thought to have a role in biological processes such as growth and development in animals, including humans and worms. But what happens in the brain to allow and maintain the state of sleep is not entirely understood, which is why a simple model system like the worm is a great place to start.
Worms have a small and well-characterized nervous system consisting of only 302 neurons. The connections between these neurons have been completely mapped so learning about the circuits, or neural networks, that control behaviors is simpler than in more complex organisms.
In contrast, humans have billions of neurons and trillions of synapses. Scientists have started to map these connections, but it will take many more years of research to achieve the complete picture.
Worm genetics are also much simpler than other animals because C. elegans exist primarily as self-fertilizing hermaphrodites, meaning they produce both sperm and eggs and can reproduce independently of a mate. Therefore, new or modified DNA can be introduced into worms to alter the expression of genes in their offspring, which allows us to create new strains of worms with relative ease.
These new strains of worms can be designed to express certain proteins in individual neurons, and/or to make the neurons glow green for imaging experiments. This helps us to identify the neurons that have a role in behaviors, such as sleep.
Just like humans, worms do not interact with their environment when they are asleep, because their sensory neurons are not able to respond to external cues such as the presence of food or odors. This is because sensory neurons are being “silenced” by the action of neuropeptides in the brain that promote the sleep state.
Neuropeptides are hormone-like chemical messengers that are released by one set of neurons to affect another set of neurons. To wake the worm up, other neuropeptides are released to wake up, or “arouse,” the worm by allowing their sensory neurons to become active again. Once awake, the worms can respond to their environment and resume normal activities such as eating and mating.
The Kaplan lab is interested in identifying which neurons play a role in this process, and the mechanisms these neuropeptides employ to create the sleep and arousal states.
We have already identified a circuit of neurons associated with sleep and arousal in worms. The goal of my project is to find additional neurons that function in this circuit, and then learn how these neurons communicate to regulate these behavioral states.
As a neuroscientist, I have always been fascinated by the complexity of the nervous system and how much is still unknown about how the brain works. Understanding the nervous system of a “simple” organism such as C. elegans can help us to deconstruct basic functions of the brain in more complex organisms.
Down the road, what we discover about worm sleep could be applicable to humans and lead to therapies that promote sleep in the brain. These tiny worms have a lot to tell us about our own brains. Even in their sleep.
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