Out in the Cold

Serotonin’s long-debated role in sleep promotion is temperature-dependent.

Mar 1, 2016
Karen Zusi

BRAINWAVES: A serotonin-depleted mouse with an electroencephalography headmount implanted to record sleep activityNICK MURRAY

EDITOR'S CHOICE IN NEUROSCIENCE

The paper
N.M. Murray et al., “Insomnia caused by serotonin depletion is due to hypothermia,” Sleep, 38:1985-93, 2015.

Sleepless nights
Early research into serotonin’s functions suggested that the neurotransmitter promotes sleep: lab animals deprived of the chemical often developed insomnia. More recent evidence indicated that serotonin plays a part in wakefulness instead, a theory that has gained significant traction. But explanations of the initial experimental data were scarce—so Nick Murray, then a research fellow at the University of Iowa Carver College of Medicine, started digging.

Faulty furnace?
“Over the past 5 or 10 years, we’ve found that serotonin is a key neurotransmitter for generating body heat,” says Murray. To investigate whether this role was related to serotonin’s impact on sleep, he and his colleagues injected para-chlorophenylalanine into mice to inhibit serotonin synthesis.

On ice
When kept at room temperature (20 °C), the mice with depleted serotonin slept less and developed a lower body temperature compared with their control counterparts. However, when housed at 33 °C—a thermoneutral temperature for mice—the sleep and body temperature of the treated mice stayed normal. “Serotonin isn’t a sleep-promoting neurotransmitter,” concludes Murray, now a resident at California Pacific Medical Center. He suggests that mice lacking serotonin had a tough time sleeping under early experimental conditions simply because the animals were cold, and that at higher temperatures other neurotransmitter systems in the brain would function to allow them a normal sleep-wake cycle.

Case closed
The study “solves a long-standing mystery” in the field, says Clifford Saper of Harvard University. “Not very many labs measure sleep and body temperature at the same time,” he adds. “It just basically escaped everybody’s notice for all these years.”