New experiments show that brain cells called VTA dopaminergic neurons are directly responsible for causing and maintaining wakefulness in mice. When these neurons are active, they create wakeful brain activity as well as promote wakeful behaviors in the mice—and suppressing the activity of these neurons also suppresses wakefulness, researchers report online September 5 in Nature Neuroscience.

Previous research has shown that these neurons are involved in motivated behavior and potentially the arousal necessary to carry out those behaviors, but until now there has been no evidence that the neurons directly cause wakefulness. The research team, led by Luis de Lecea, Ph.D., a 2008 Independent Investigator and 2012 Distinguished Investigator grantee, concludes that there is a fundamental role in the sleep-wake cycle for these neurons, which boost brain activity related to the chemical messenger dopamine.

Many psychiatric disorders including major depression, schizophrenia, and bipolar disorder are characterized by irregular dopamine signaling and sleep cycles, and these new findings may help to clarify the relationship between these two types of symptoms, was also on the research team.

When the scientists suppressed the VTA dopaminergic neurons in mice, they found that the mice were more likely to fall asleep, to stay asleep, and pursue sleep-related behaviors like nest-building. They also determined that it was necessary to have these neurons active for mice to maintain wakefulness in the face of important stimuli like opportunities to eat, mate, and avoid predators. The team also used optogenetic methods, which manipulate brain cell activity using a fiber optic light source, to show that stimulating VTA dopaminergic neurons can jump-start and maintain wakefulness in mice, suppressing sleep and nesting behavior.