No sedative necessary: Scientists discover new “sleep node” in the brain

A sleep-promoting circuit located deep in the primitive brainstem has revealed how we fall into deep sleep. Discovered by researchers at Harvard School of Medicine and the University at Buffalo School of Medicine and Biomedical Sciences, this is only the second “sleep node” identified in the mammalian brain whose activity appears to be both necessary and sufficient to produce deep sleep.

Published online in August in Nature Neuroscience, the study demonstrates that fully half of all of the brain’s sleep-promoting activity originates from the parafacial zone (PZ) in the brainstem. The brainstem is a primordial part of the brain that regulates basic functions necessary for survival, 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 Caroline E. Bass, assistant professor of Pharmacology and Toxicology in the UB School of Medicine and Biomedical Sciences and a co-author on the paper.

The researchers found that a specific type of neuron in the PZ that makes the neurotransmitter gamma-aminobutyric acid (GABA) is responsible for deep sleep. They used a set of innovative tools to precisely control these neurons remotely, in essence giving them the ability to turn the neurons on and off at will.

“These new molecular approaches allow unprecedented control over brain function at the cellular level,” says Christelle Ancelet, postdoctoral fellow at Harvard School of Medicine. “Before these tools were developed, we often used ‘electrical stimulation’ to activate a region, but the problem is that doing so stimulates everything the electrode touches and even surrounding areas it didn’t. It was a sledgehammer approach, when what we needed was a scalpel.”

“To get the precision required for these experiments, we introduced a virus into the PZ that expressed a ‘designer’ receptor on GABA neurons only but didn’t otherwise alter brain function,” explains Patrick Fuller, assistant professor at Harvard and senior author on the paper. “When we turned on the GABA neurons in the PZ, the animals quickly fell into a deep sleep without the use of sedatives or sleep aids.”

Comparisons of vertebrate, mammalian central nervous systems to those of non-mammalian vertebrates shows that both types of brains have very similar patterns of cell groupings and connections. While brains of different species are specialized for certain types of tasks that allow the animal to survive in their particular niche, it is fascinating to realize that all vertebrate central nervous systems have a common organization.

Thus, whether looking at a cat, a rat, a human, a monkey, a bird or a fish, if you understand the organization of the brain of one species, the brain of another vertebrate should seem very familiar to you. Even the brains of animals that do not share a common ancestor may be very similar because animals share a common environmental challenge. For example, animals that need to root for food such as sharks, alligators and pigs will all have a great deal of sensory innervation to the snout area. Animals that use olfaction to find food, prey, mates and avoid predators will have a highly developed olfactory system.