Nematode brains offer window into human sleep problems

Next time you have trouble sleeping, don’t count sheep. Just ponder the idea that the neurons in your brain could be firing like those in roundworms randomly searching for food.

That connection is proposed in a theoretical neuroscience paper that emerged from 14 years of research led by Shawn R. Lockery, a professor in the UO’s Department of Biology. The paper, which has 12 co-authors from 10 institutions, published this week in the journal eLife.

As humans sleep, neurons fire randomly in between brief, alternating states of wakefulness and sleep. Such fragmentation is heightened in sleep disorders.

The fragmentation found in the tiny nematodes used in the research offers a new framework to identify genetic and physiological activities of the neural circuitry involved in sleep, the research team concluded. The nematode brain is tiny, containing just 302 neurons, making it a simple model to study, Lockery said.

“Our field has a complete wiring diagram of this worm’s brain,” said Lockery, also a member of the Institute of Neuroscience. “You can find the same neuron in any animal you look into and learn to understand how individual neurons function.”

Researchers in Lockery’s lab tested the predictability of mathematically driven equations about random search strategies in the brain. To do so, the worms were removed from access to their usual food — bacteria in rotting vegetables — and placed on clean petri dishes with no sensory clues as to where a meal is located.

Initially, the movements of the worms and the neural networks involved were mapped as the worms crawled forward, paused, reversed and then resumed their search in another direction.

“Every animal faces the need to find food,” Lockery said. “In some instances food is undetectable until you basically fall on it: Birds looking for marine invertebrates in the sand will move about and peck until they find their meal. This is called random search.”

Humans, too, from hunter-gatherers to those who engage in technologically advanced fishing, exhibit similar random-search behaviors but, “no one has known how the nervous system controls this,” Lockery said.

With the mapping done, researchers used lasers to knock out neurons. They expected the worms to spend more time in reverse when neurons linked to forward movement were eliminated, or vice versa. Instead, the reaction was symmetrical. Shorter times were found in both forward and reverse movements.

“There are centers in the human brain stem that promote wakefulness and sleep,” Lockery said. “They are coupled just like the system we see in the worms. This involves clusters of neurons that are fighting against each other to be active. We constantly wake up and go back to sleep, but we don’t remember it. Sleep is random, just the way the worm’s movement is.”

Researchers have done similar experiments in rats and mice where neurons related to sleep states were manipulated. The findings are consistent.

“The same paradoxical effect that we found in our worms also occurs in these other organisms,” Lockery said. “This line of research suggests that we now have a simple way to try to understand how this fragmentation occurs. That’s the first step in understanding how medical science might be able to pursue therapeutics that could mitigate extreme cases of fragmentation.”

The National Institutes of Health supported the research. UO co-authors are William M. Roberts, biology professor emeritus, and Serge Faumont, a senior research associate in the Institute of Neuroscience.

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