Researchers identify Brain's "sleep switch"

Two decades ago, Clifford Saper, MD, director of the department of neurology at the Beth Israel Deaconess Medical Center (BIDMC), and his colleagues discovered a set of nerve cells that, in their opinion, could be the switch that allows the brain to disconnect, allowing him to sleep. In a new study published in Nature CommunicationsSaper and his colleagues demonstrate to mice that these cells, located in a region of the hypothalamus called the Ventrolateral Preoptic Nucleus (VLPO), are actually essential for normal sleep.

"Our article is the first test of what happens when you activate VLPO neurons," said Saper, also a professor at Harvard Medical School. "The results confirm our initial observation that VLPO cells are essential for normal sleep."

By working with genetically modified mice, the Saper team artificially activated VLPO neurons with the help of several different tools. In a set of experiments, scientists activated neuronal cells with the help of a laser light beam to light them, a process called optogentics. In another test, the team used a chemical to selectively activate VLPO neurons. In both cases, the activation of these cells led to deep sleep.

The results confirmed earlier findings by Saper and colleagues that these neurons are active during sleep and that the damage caused causes insomnia – as Saper's subsequent work on laboratory animals demonstrates, and 2014, in older people having lost VLPO cells from the natural aging process.

Based on this earlier work, another team of researchers has announced the opposite. In a 2017 publication, experiments stimulating VLPO neurons woke up laboratory animals. In their current article, Saper's team has cleared this apparent contradiction.

"We found that when VLPO cells are stimulated one to four times a second, they trigger each time they are, resulting in restful sleep," Saper said. "But if you stimulate them faster than that, they start pulling no more and stop pulling in. We learned that our colleagues in the other lab stimulated the cells 10 times a second, which cut them off. "

In addition, the Saper team also found that VLPO cell activation caused a drop in body temperature. Scientists already knew that warm temperatures activate VLPO cells and that body temperature drops slightly during sleep when VLPO neurons are triggered.

"We thought it was the reason why people had to put themselves under a warm blanket to fall asleep," Saper added.

However, with continued activation, body temperature in mice dropped to five or six degrees Celsius. Saper's team suggested that excessive firing of these same neurons could be responsible for prolonged sleep and lower body temperature in hibernating animals. As a follow-up, the Saper team is already studying the relationship between sleep and body temperature in the context of ongoing studies.