Contrary to what many Hopkins students seem to believe, a good night’s sleep is essential for optimal physical, mental and emotional functioning. Despite the recognized importance of sleep, the brain structures responsible for sleep regulation are still relatively unfamiliar territory. However, several research pioneers have started blazing the trail into the wilderness of the neuroscience of sleep.
Researchers at the Harvard School of Medicine and the University of Buffalo School of Medicine & Biomedical Sciences have discovered a sleep-promoting circuit located within the depths of the primitive brainstem that sheds some light on how we fall into deep sleep. Deep sleep is still relatively uncharted scientific territory. The researchers’ discovery is only the second structure identified in the mammalian brain whose activity seems to be both necessary and sufficient to initiate deep sleep. The study was published online in Nature Neuroscience on Aug. 17.
The researchers found that a grand total of half of all of the brain’s sleep-promoting activity originates from a region called the parafacial zone (PZ), located in the brainstem. The brainstem, which consists of the medulla oblongata, the pons and the midbrain, is located in the posterior region of the brain and is structurally continuous with the spinal cord.
A small organ with big responsibilities, the brainstem regulates many basic functions essential to survival, including heart rate, breathing, blood pressure, body temperature and sleeping. According to the researchers, this close connection of a vital sleep center with other brain regions that are essential for life emphasizes the evolutionary significance of sleep in the brain.
The researchers discovered that a specific type of GABA-producing neuron in the PZ is responsible for producing deep sleep. GABA, short for gamma-aminobutyric acid, is the chief inhibitory neurotransmitter in the mammalian central nervous system. In addition to reducing neuronal excitability, GABA is also directly responsible for regulating muscle tone in humans. Neurons that produce GABA are called GABAergic neurons.
In order to perform the experiments, the researchers introduced a virus into the PZ that expressed a “designer” receptor on only GABAergic neurons but did not otherwise modify brain function. This allowed the researchers to achieve the degree of precision required for the experiments. They could switch the neurons “on” and “off” as needed. The researchers discovered that when they switched “on” the GABAergic neurons in the PZ of mice, the animals rapidly fell into a deep sleep without the use of sedatives or sleep aids.
According to the researchers, this fresh molecular-level approach gave them unprecedented control over cellular-level brain function. Prior to the advent of the novel tools used in the study, the researchers frequently relied on electrical stimulation to activate regions of the brain. However, the problem with this approach is that the electrode used will stimulate everything it touches and even surrounding areas it doesn’t touch. In other words, the electrical stimulation method is akin to firing a cannon to swat a fly.
This discovery is a major breakthrough in understanding the science of deep sleep, but much work remains to be done. According to the researchers, exactly how these GABAergic neurons interact with other sleep- and wake-promoting regions of the brain still needs to be studied. But the future looks bright. The researchers hope that eventually their findings may be used to develop new medications for treating sleep disorders, such as insomnia, as well as safer and more effective anesthetics.
