A study led by Harvard Medical School researchers at VA Boston Healthcare System offers critical clues into one of the most confounding questions in sleep biology: How is deep sleep regulated by the brain?
The work, conducted in mice and published in Nature Communications, identifies an area in the brain that regulates the oscillations of delta waves—electrical signals transmitted across neurons that arise during the deepest phases of relaxation. They are a hallmark of restorative sleep.
The research team homed in on neurons in the thalamus, a region of the brain that regulates sleep and wakefulness, among other functions. Using CRISPR-Cas9 gene editing, the researchers disrupted a gene that codes for a protein that binds the inhibitory neurotransmitter GABA. The protein is a target of drugs that promote sleep. Disruption of this gene in mouse models boosted the activity of delta waves and enhanced deep sleep in the animals.
If replicated in further animal models, investigators say the findings could lay the groundwork for designing therapies that precision-target this protein to induce deep sleep.
“Our findings represent an important step forward in pinpointing the molecular basis of sleep regulation and point to an alternative pharmacologic strategy for promoting natural, restorative sleep,” says Radhika Basheer, PhD, study senior investigator and associate professor of psychiatry at Harvard Medical School and VA Boston Healthcare System, in a press release.
New therapies are sorely needed, according to the release. Commonly used insomnia medicines, while an important tool for treatment of persistent insomnia, have well-known drawbacks. Many of these medications work by getting people to fall asleep fast, but they also tend to dampen the activity of restorative delta waves. Thus, while such medications promote falling asleep, the slumber they induce is not necessarily restorative.
“We believe our findings set the stage for developing a new class of sleep medicines that can achieve this all-important maintenance of deep sleep by boosting delta wave oscillations,” says Basheer in the release.