The switch that says it’s time to sleep

February 19, 2014

A small group of neurons put flies to sleep when they need to rest.

The body uses two mechanisms to regulate sleep. One is the body clock, which attunes humans and animals to the 24 hour cycle of day and night. The other mechanism is the sleep ‘homeostat’: a device in the brain that keeps track of your waking activity and puts you to sleep when you are tired and need to reset. This mechanism is purely internal. When it malfunctions, sleep deficits build up.

Over the past half-century, scientists have learned what precisely makes the circadian clock tick. The crucial insight came in 1971 with the discovery of mutant fruit flies whose clocks were abnormally fast or slow. In a study published in the journal Neuron, CNCB scientists now lift the curtain on the second master regulator of sleep: the homeostat.

Once again, fruit flies provided the critical clue, in the form of a molecular piece of the homeostatic sleep switch. ‘Mutating this gene leads to insomnia-like symptoms. Because of their inability to sleep normally, mutant flies have severe learning and memory deficits, much like people do after staying awake all night’ says Jeff Donlea, one of the lead authors of the study.

The switch works by regulating the activity of a handful of neurons in the brain that were previously found to promote sleep. The neurons become more responsive when we’re tired and need sleep, and then dampen down when we’re fully rested.

‘The sleep homeostat does something similar, in principle, to the thermostat in your home,’ says Gero Miesenböck, in whose lab the new research was performed. ‘A thermostat measures temperature and switches on the heating if it’s too cold. The sleep homeostat measures how long you have been awake and puts you to sleep if you exceed your limit.’

The sleep mechanism is likely to be relevant to humans. Donlea explains: ‘There is a similar group of neurons in a region of the human brain. These neurons are also electrically active during sleep and, like the flies’ cells, are the targets of general anaesthetics. It’s therefore likely that a molecular mechanism similar to the one we have discovered also operates in humans.’

The researchers say that pinpointing the sleep switch might help us identify new targets for novel drugs – potentially to improve treatments for sleep disorders.

But there is much still to find out, and further research could give insight into the mystery of why we need to sleep at all. ‘The big question now is to figure out what internal signal the sleep switch responds to,’ says Diogo Pimentel, the other lead author of the study. ‘What do these sleep-promoting cells monitor while we are awake?

‘If we knew what changes in the brain during waking that requires sleep to reset, we might get closer to understanding why all animals need to sleep.’


Neuronal Machinery of Sleep Homeostasis in Drosophilaby Jeffrey M. Donlea, Diogo Pimentel and Gero Miesenböck. Neuron 81: 860–872 (February 19, 2014).