A brain circuit has been identified by scientists from Stanford University School of Medicine. The said circuit is believed to play a crucial role in the sleep-wake pattern. It is said to play an important role in the reward system, which can be described as interconnected pathways that are important for promoting certain behaviors in humans as well as animals in order to produce and survive.
The current results made sense for the scientific world as the sleep-wake cycle and goal-directed behaviors (running away from danger, and looking for food, etc.) were believed to have some sort of coordination with each other. Individuals can’t look for food unless they sleepwalk. In the same manner people are better at getting up from bed when they’re looking forward to the day ahead.
According to Luis de Lecea, PhD, senior author of the study, and a professor of psychiatry and behavioral sciences, before the current study there wasn’t a pinpointed anatomical location showing the integration of brain’s arousal and reward systems.
The current study was published in Nature Neuroscience. Dr. de Lecea went on to say that the results have “potential huge clinical relevance”. A sleep disorder, insomnia, is a multibillion pharmaceutical market. This disorder is treated by benzodiazepines that shut down the whole brain nonspecifically. However, because of these results new therapies can be created for targeting the identified circuit for promoting higher-quality of sleep.
According to the National Institutes of Health, around 25-30% of U.S. adults suffer from sleep disturbances. It has also been seen that disturbed sleep-wake rhythms can give rise to various neuropsychiatric disorders. It should be noted that all vertebrates (fish, frogs, humans, etc.) have a similar reward system circuitry. This circuit makes use of dopamine to function properly.
Ada Eban-Rothschild, PhD, the lead author of the current study said that “Since many reward-circuit-activating drugs such as amphetamines that work by stimulating dopamine secretion also keep users awake, it’s natural to ask if dopamine plays a key role in the sleep-wake cycle as well as in reward. But, in part due to existing technical limitations, earlier experimental literature has unearthed little evidence for the connection and, in fact, has suggested that this circuit probably wasn’t so important.”
Male laboratory mice were used for the purpose of this study. The mice were bioengineered in different ways in order to use technologies for remotely suppressing, exciting, and monitoring the dopamine-secreting nerve cells from the VTA of the mice. The relative stages of being asleep or aroused were determined by measuring the overall brain activity and muscle tone of the mice. Researchers viewed the behavior of mice through video cameras.
The results saw a rise in the dopamine-secreting nerve cells emanating from the VTA. The levels stayed elevated while the mice remained awake. A reduction was seen when mice were preparing to sleep, and stayed low while they slept. Raising the nerve-cell population in the animals urged them to remain awake even when they should be sleeping with regards to their diurnal cycle. The control mice, whose VTA activity wasn’t manipulated, ended up building nests (using materials placed in their cages) and falling asleep.
Suppressing the nerve-cell population showed that mice, even during the active period of their 24-hour cycle, would fall asleep even in the presence of triggers that included delicious food, fear-inducing fox urine, and females.
According to Dr. Eban-Rothschild the actions that were linked to mice building nests had an association with a reduction in their VTA activity. While on the other hand higher levels of VTA activity was associated with non-nest building behavior. She further added that “We knew stimulating the brain’s dopamine-related circuitry would increase goal-directed behaviors such as food- and sex-seeking. But the new study shows that at least one complex behavior is induced not by stimulating, but by inhibiting, this very circuit. Interestingly, this behavior — nest building — is essential to a mouse’s preparation for sleep.”
Dr. Eban-Rothschild said that similar patterns might be seen in humans too with regards to having a sleep-preparations starter site. If individuals disturb this ‘preparation’ then it might amp up emotions, induce high levels of VTA dopamine, and prevent a person from falling asleep.
“We have plenty of drugs that counter dopamine,” said Dr. de Lecea. “Perhaps giving a person the right dose, at just the right time, of a drug with just the right pharmacokinetic properties so its effect will wear off at the right time would work a lot better than bombarding the brain with benzodiazepines, such as Valium, that knock out the entire brain.”
He further added that the results might help to create drugs that specifically target VTA’s dopamine secreting nerve cells to aid individuals suffering from schizophrenia or bipolar disorder i.e. neurological conditions which are characterized by disturbances in the sleep-wake cycle.