Sleep promoting brain cells identified

Washington

Scientists have identified a type of neuron that promote sleep, an advance that can help develop novel drugs to treat sleep disorders.

Researchers at John Hopkins University in the US identified brain cells, located in a part of the hypothalamus called the zona incerta.

These cells could offer novel drug targets to treat sleep disorders, such as insomnia and narcolepsy, caused by the dysfunction of sleep-regulating neurons, they said.

The team described neurons that express a gene called Lhx6. Lhx6-expressing cells have not been observed in this area of the brain before and appear to connect the zona incerta to areas of the brain that control sleep and wakefulness, researchers said.

“We know cells in other regions of the brain use Lhx6 and that the gene is vital for these areas to develop properly.

For example, disrupting Lhx6 expression can result in many diseases, including severe epilepsy,” said Seth Blackshaw, professor at John Hopkins University.

Normal sleep has two parts, rapid eye movement (REM) and nonrapid eye movement (non-REM). REM sleep is where most dreaming occurs, while non-REM sleep is understood to be deeper and less active. Both parts are essential for healthy, restful sleep.

Researchers used artificial receptors called designer receptors exclusively activated by designer drugs to increase the activity of Lhx6-expressing neuronsin mice and observed their behaviour.

They observed that when the neurons were activated, there was an increase in both REM and non-REM sleep for eight hours following treatment.

One population of cells connected to the Lhx6-expressing cells are neurons that are known to secrete hypocretin, a signal that promotes and sustains wakefulness, and which is disrupted in narcolepsy, researchers said.

Using drugs that block hypocretin action, they then showed that the increase in non-REM sleep seen following activation of Lhx6-expressing cells was dependent on hypocretin, but that the increase in REM sleep was not.

“This shows that Lhx6 inhibits not only hypocretin- producing cells, but also other types of wake-promoting cells,” said Kai Liu, a graduate student at the Johns Hopkins University School.

“The fact that these neurons expressing Lhx6 promote both non-REM and REM sleep distinguishes them from other sleep- regulating cells. They present a new target for treating a broad range of sleep disorders,” said Blackshaw.

The study was published in the journal Nature.