In a fascinating new investigation, scientists from the Harvard School of Medicine and the University of Buffalo School of Medicine and Biomedical Sciences have discovered a “sleep node” in the mammalian brain responsible for sending us into deep sleep.
The team found that a specific neuron in the brainstem’s parafacial zone (PZ) makes the neurotransmitter gamma-aminobutyric acid (GABA), which is responsible for inducing deep sleep. Next, they investigated whether it was possible to control these neurons by switching them on and off remotely.
To do so required the deployment of groundbreaking new tools. “These new molecular approaches allow unprecedented control over brain function at the cellular level,” says Dr. Christelle Ancelet, postdoctoral fellow at Harvard School of Medicine.
She explains:
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.
The level of precision required for this molecular control required the team to design innovative solutions. This included introducing a virus into the PZ expressing a “designer” receptor that only affected GABA neurons. Apart from the interaction with the GABA neurons, brain functions were otherwise unaltered.
Testing this designer virus in a mouse model, the researchers witnessed immediate results. “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,” says senior author and Harvard assistant professor Dr. Patrick Fuller.
Further research will investigate mechanism behind sleep neurons
Although the team reports success in their attempts to switch this sleep node on and off, they have yet to pinpoint the exact interaction between these sleep neurons and “other sleep and wake-promoting brain regions.”
The authors, who published their results in the journal Nature Neuroscience, suggest that their findings may eventually translate into new pharmacological treatments for sleep disorders, as well as potentially better and safer anesthetics.
“We are at a truly transformative point in neuroscience, where the use of designer genes gives us unprecedented ability to control the brain,” says co-author Dr. Caroline E. Bass, assistant professor of Pharmacology and Toxicology at the UB School of Medicine and Biomedical Sciences. “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.”
Earlier this year, scientists at Penn Medicine in Philadelphia, PA, published a study in The Journal of Neuroscience suggesting that sleep deprivation may lead to irreversible physical damage and loss of brain cells.
In a mouse model, the Penn researchers found that extended wakefulness inhibited the response of a protein that plays a critical role in producing mitochondrial energy and protecting neurons from metabolic injury. After the mice endured several days of sleep patterns configured to resemble shift workers, the team observed a 25 percent loss of the neurons that regulate this protein, as well as increased cell death.
Similar damage has been documented in humans, as well. For instance, in a study published earlier this month, researchers from Oxford University found that sleep deprivation is associated with loss of brain volume. Using a series of brain imaging studies, the Oxford team discovered that individuals with poor sleep quality had more rapid, widespread decline in brain volume across multiple regions, including the frontal, temporal and parietal areas, with effects more evident in those over the age of 60.