Australasian Science: Australia's authority on science since 1938

The Sleep Switch

By Tim Hannan

Researchers have located a brain circuit that regulates sleep and wakefulness.

Sleep is often described as one of the three pillars of a healthy life, along with regular exercise and a balanced diet. Yet while studies have consistently demonstrated the detrimental effects of poor sleep on physical and mental well-being, much less is known about the processes that regulate sleep and wakefulness, including the location and interaction of the neurobiological mechanisms critical to the initiation of sleep.

Delegates to the annual conference of the Australasian Sleep Association (ASA) held this month in Adelaide will be discussing the findings of a new study that has identified a specific brain circuit that drives sleep–wake states. As the ASA President Dr Maree Barnes summarised, “sleep researchers have long been looking for the key to what makes us sleep and what keeps us awake. Scientists at Stanford University have now moved one step closer to discovering this switch – the dopamine-secreting neurons of the ventral tegmental area.”

It had long been suspected that the brain regions that drive goal-directed behaviours and those that regulate sleep must be coordinated in some way. However, the precise location of the mechanism involved in this interaction between reward and arousal systems had not been identified.

In the study, published last month in Nature Neuroscience, Ada Eban-Rothschild and colleagues at Stanford University based their investigations on two well-established findings. First, the neurotransmitter dopamine was known to be involved in the functioning of the brain’s reward systems, which include the nucleus accumbens, a forebrain structure particularly implicated in generating feelings of pleasure in anticipation of, or response to, obtaining a desired objective. Second, previous research had linked the dopamine-stimulating effects of amphetamines to increased wakefulness in users.

These twin findings prompted the researchers to explore one particular region, the ventral tegmental area (VTA), from which numerous dopamine-secreting nerve fibre tracts run to different parts of the brain, including the nucleus accumbens.

The researchers observed the activity of the dopamine-secreting nerve cells in the VTA of mice, and noted that activity in these cells increased when mice woke from sleep, and remained high while awake. After a period of activity, the mice built nests from the various materials placed in their cages and, on completion, dropped off to sleep.

The researchers then experimentally excited or suppressed the activity in the dopamine-secreting nerve cells of the VTA, and measured the mice’s general arousal and overall brain activity.

When the region was activated, the mice were roused and remained awake for unusually long periods.

When activity in these cells was suppressed, the mice’s level of activity decreased. They then engaged in a nest-building and fell asleep, even remaining asleep through exposure to common triggers of arousal such as food, the presence of a female mouse or the smell of fox urine.

The findings suggest that a “sleep preparation state” is induced by activity in the dopamine-secreting cells of the VTA.

It is known that emotional arousal or exposure to bright light delays movement into the sleep preparation state, and it may be speculated that these activities produce this effect by stimulation of the VTA. Conversely, inhibition of the VTA cells appears to assist organisms to move into the sleep preparation state. This finding offers the possibility of directly targeting sleep problems in humans.

Commenting on the study, Barnes stated: “This exciting research may lead to better treatments for patients with sleep disorders such as idiopathic hypersomnia and chronic insomnia, debilitating diseases which affect up to one-third of adult Australians. Currently, many patients with insomnia are treated with sedative hypnotics, drugs which have significant side-effects and poor long-term effectiveness.” The potential benefit, she noted, was that “inhibition of the VTA may lead to better and safer treatments.

We look forward to more work in this area.”

A/Prof Tim Hannan is Head of the School of Psychology at Charles Sturt University, and the Past President of the Australian Psychological Society.