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.

One of the persistent ideas in biology and comparative psychology has been that evolution is a progressive process so that we can arrange species into a hierarchy from “lower”, less complex species all the way up to “higher” more complex species, with humans occupying the highest rung of the ladder. The implication of this is that lower, less complex forms came first and there has been a progressive evolution to produce the ‘most evolved’ form of animal, the human. Philosophically, this is a very comforting thought for humans, since this philosophy suggests that the meaning of human existence is to be the most developed, complex and intelligent species on the earth. However, current thought suggests that this kind of thinking is anthropocentric and has no scientific value. It is a human concept, not a biological principle. Thus, it is not appropriate to refer to animals as ‘higher’ or ‘lower’ on the evolutionary scale. What is appropriate is to talk about some characteristics in a species being more ‘primitive’, with the word primitive meaning that that characteristic developed longer ago than some other characteristic. Indeed, we can even challenge the idea that primates are more complex than other species. Even a fairly cursory look at a number of what we think of as less complex species indicates that many non-mammals have more sensitive olfaction (including smelling molecules that primates cannot), more sensitive visual systems (including detection of colors, UV, infrared and polarized light that primates cannot see), and that some species generate electrical fields that cannot be detected by mammals. Thus, complexity is not only found in mammals.

All that said, when looking at reptiles, fish, birds and mammals, there seems to be a general trend (with some overlap) for vertebrates to develop larger brains as we move from more primitive vertebrates to less primitive vertebrates. What is clear, is that a less complex CNS can work well for animals that occupy less complex environmental niches, while some vertebrates have evolved more complex brains to allow them to utilize more complex and variable niches in the environment. The development of a more complex brain can simply be thought of as an adaptation, since cognition (such as learning, memory and decision making), enhanced sensory ability and improved motor control all follow from developing a more complex CNS. In turn, these abilities aid in survival. Adaptations for larger, more complex brains have resulted in:

  increased numbers of neurons
  more extensive dendritic organization
  more synapses
  more efficient arrangement of neurons

No sedative necessary: Scientists discover new “sleep node” in the brain' How these neurons interact in the brain with other sleep and wake-promoting brain regions still need to be studied, the researchers say, but eventually these findings may translate into new medications for treating sleep disorders, including insomnia, and the development of better and safer anesthetics.

“We are at a truly transformative point in neuroscience,” says Bass, “where the use of designer genes gives us unprecedented ability to control the brain. 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 work was funded by the National Institutes of Health.

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