Published October 17, 2014
University at Buffalo researchers have helped discover a sleep-promoting circuit in the brainstem, revealing how we fall into deep sleep — findings that may lead to new therapies for sleep disorders.
This is only the second sleep node identified in the mammalian brain that appears to be both necessary and sufficient to produce deep sleep.
The study, “The GABAergic Parafacial Zone is a Medullary Slow Wave Sleep–Promoting Center,” has been published in Nature Neuroscience.
The study, a collaborative effort between Harvard School of Medicine and UB, shows that a type of neuron in the parafacial zone (PZ) — which makes the neurotransmitter gamma-aminobutyric acid (GABA) — is responsible for deep sleep.
Using a set of innovative tools to precisely control these neurons remotely, the researchers were able to turn them on and off at will.
To achieve the necessary precision, the researchers introduced a virus into the PZ that expressed a “designer” receptor on only GABA neurons but didn’t otherwise alter brain function.
When the researchers turned on the GABA neurons in the PZ, the animals quickly fell into a deep sleep without the use of sedatives or sleep aids.
“The use of designer genes gives us unprecedented ability to control the brain,” says Bass.
“We can now answer fundamental questions of brain function which have traditionally been beyond our reach, including the ‘why’ of sleep, one of the more enduring mysteries in the neurosciences.”
The new molecular approaches allow control over brain function at the cellular level, explains first author Christelle Anaclet, PhD, postdoctoral fellow at Harvard.
“Before these tools were developed, we often used ‘electrical stimulation’ to activate a region, but doing so stimulated everything the electrode touched and even surrounding areas it didn’t,” says Anaclet.
“It was a sledgehammer approach, when what we needed was a scalpel.”
Further study is needed to learn how the neurons interact with other sleep- and wake-promoting brain regions, the researchers say.
Eventually these findings may translate into new medications for treating sleep disorders, including insomnia, as well as better, safer anesthetics.
The study demonstrates that half of all of the brain’s sleep-promoting activity originates from the PZ in the brainstem — the area regulating basic survival functions such as breathing, blood pressure, heart rate and body temperature.
“The close association of a sleep center with other regions that are critical for life highlights the evolutionary importance of sleep in the brain,” says Bass.
The work has been funded by the National Institutes of Health.