Sleep and wakefulness are partly controlled by an internal biological clock. However, the mechanisms that allow this clock to act on brain circuits remain poorly understood. Scientists at the University of Geneva (UNIGE) have identified, in the fruit fly Drosophila melanogaster, a neural circuit linking the biological clock to a region of the brain involved in sleep and wakefulness. Their findings, published in the journal Current Biology, shed light on how the rhythms generated by the biological clock are translated into neuronal activity to coordinate complex behaviours such as sleep.
The circadian clock is an internal biological system that regulates sleep-wake cycles, as well as many physiological functions such as body temperature and hormone production. In many animals, this clock relies on a network of neurons that generates rhythms of approximately 24 hours.
These neurons must then transmit this information to other regions of the brain allowing activity and behaviour to be adapted to the time of day. However, the specific neurons involved and the mechanisms that allow the clock to influence brain circuits remain poorly understood.
Emi Nagoshi’s laboratory, at the Section of Biology of the UNIGE Faculty of Science, uses the fruit fly, the small ‘vinegar fly’ attracted to ripe fruit, to study these mechanisms in detail. Using genetic mapping of connections between neurons, the scientists identified the nerve cells located downstream of the biological clock neurons.
A circuit linking the biological clock to wakefulness
Imaging techniques that measure neuronal activity allowed the researchers to show that this activity varies throughout the day. They identified a connection between the biological clock neurons and a population of neurons that produce dopamine, a molecule that enables neurons to communicate with one another.
“We observed that the clock neurons inhibit these dopaminergic neurons, which in turn stimulate neurons in the mushroom body. This brain region plays a role in learning, memory and the regulation of sleep, and its activity contributes to promoting wakefulness during the day,” explain Blanca Lago Solis and Rafael Koch, postdoctoral researcher and research associate in Emi Nagoshi’s group.
When the clock neurons inhibit the dopaminergic neurons, the wake-promoting signal decreases. Conversely, when this inhibition is released, the dopaminergic neurons can more strongly stimulate the mushroom body and promote wakefulness. Through its neurons, the biological clock can therefore transmit information about the time of day to a brain circuit involved in regulating sleep and wakefulness.
These findings shed light on how the biological clock influences sleep and wake states. In particular, they highlight the central role of dopamine in promoting wakefulness and show how information from the biological clock is relayed through different neural circuits throughout the day.
Disruptions of the circadian clock are associated with various sleep disorders and alterations in brain function. A better understanding of these fundamental mechanisms could ultimately help explain how disturbances in biological rhythms affect the brain.