Researchers Discover Sandman’s Role in Sleep Control

Summary: A new study brings researchers one step closer to unlocking the mysteries of sleep.

Source: University of Oxford.

Oxford University researchers have discovered what causes a switch to flip in our brains and wake us up. The discovery, published in the journal Nature, brings us closer to understanding the mystery of sleep.

Sleep is governed by two systems—the circadian clock and the sleep homeostat. While the circadian clock is quite well understood, very little is known about the sleep homeostat.

Professor Gero Miesenböck, in whose laboratory the new research was conducted, explained: ‘The circadian clock allows us to anticipate predictable changes in our environment that are caused by the Earth’s rotation. As such, it makes sure we do our sleeping when it hurts us least, but it doesn’t speak to the mystery of why we need to sleep in the first place.

‘That explanation will likely come from understanding the second controller—called the sleep homeostat. The homeostat measures something—and we don’t know what that something is—that happens in our brains while we are awake, and when that something hits a certain ceiling, we go to sleep. The system is reset during sleep, and the cycle begins anew when we wake up.’

Image shows a dial.

Image illustrating the concept of the sleep homeostat. NeuroscienceNews.com image is credited to Centre for Neural Circuits and Behaviour.

The team studied the sleep homeostat in the brain of fruit flies—the animal that also provided the first insights into circadian timekeeping, some 45 years ago. Each fly has around two dozen sleep-control neurons, brain cells that are also found in other animals and believed to exist in people. These neurons convey the output of the sleep homeostat: If the neurons are electrically active, the fly is asleep, and when they are silent, the fly is awake.

To switch the neurons the team relied on a technique called optogenetics, discovered by Miesenböck in 2002, in which pulses of light are used to switch on and off the activity of brain cells. In the current work, optogenetics was used to stimulate the production of the messenger chemical dopamine.

In people, drugs that act as psychostimulants (such as cocaine) increase dopamine levels in the brain, and this effect was also seen in the flies. When the dopaminergic system was activated, the sleep-control neurons fell silent and the fly woke up. If the team stopped the dopamine delivery and waited for a while, the sleep-control neuron flipped back to the electrically active state and the fly went back to sleep.

The sleep switch is a ‘hard’ switch, meaning that it is either on or off. ‘That makes sense,’ said Miesenböck. ‘You want to be either asleep or awake but not drift through twilight states.’

Dr Diogo Pimentel, one of the two lead authors of the study, said: ‘Being able to operate the sleep switch at will has given us a chance to find out how it works.’

When sleep-control neurons are electrically active, an ion channel the researchers discovered and called Sandman is kept inside. Ion channels control the electrical impulses through which brain cells communicate. When dopamine is present, it causes Sandman to move to the outside of the cell. Sandman then effectively short-circuits the neurons and shuts them off—leading to wakefulness.

Lead author Dr Jeff Donlea said: ‘In principle, this is a device that’s similar to the thermostat on the wall of your living room. But instead of measuring temperature and turning on the heat when it is too cold, this device turns on sleep when your sleep need exceeds a set point.’

As Prof. Miesenböck explained: ‘The billion-dollar question in all of this is: what is the equivalent of temperature in this system? In other words, what does the sleep homeostat measure? If we knew the answer, we’d be one giant step closer to unraveling the mystery of sleep.’

About this neuroscience research article

Source: University of Oxford
Image Source: This NeuroscienceNews.com image is credited to Centre for Neural Circuits and Behaviour.
Video Source: The video is credited to CNCB.
Original Research: Abstract for “Operation of a homeostatic sleep switch” by Diogo Pimentel, Jeffrey M. Donlea, Clifford B. Talbot, Seoho M. Song, Alexander J. F. Thurston and Gero Miesenböck in Nature. Published online August 3 2016 doi:10.1038/nature19055

Cite This NeuroscienceNews.com Article
University of Oxford. “Researchers Discover Sandman’s Role in Sleep Control.” NeuroscienceNews. NeuroscienceNews, 3 August 2016.
<http://neurosciencenews.com/sandman-sleep-control-4774/>.
University of Oxford. (2016, August 3). Researchers Discover Sandman’s Role in Sleep Control. NeuroscienceNew. Retrieved August 3, 2016 from http://neurosciencenews.com/sandman-sleep-control-4774/
University of Oxford. “Researchers Discover Sandman’s Role in Sleep Control.” http://neurosciencenews.com/sandman-sleep-control-4774/ (accessed August 3, 2016).

Abstract

Operation of a homeostatic sleep switch

Sleep disconnects animals from the external world, at considerable risks and costs that must be offset by a vital benefit. Insight into this mysterious benefit will come from understanding sleep homeostasis: to monitor sleep need, an internal bookkeeper must track physiological changes that are linked to the core function of sleep. In Drosophila, a crucial component of the machinery for sleep homeostasis is a cluster of neurons innervating the dorsal fan-shaped body (dFB) of the central complex. Artificial activation of these cells induces sleep, whereas reductions in excitability cause insomnia. dFB neurons in sleep-deprived flies tend to be electrically active, with high input resistances and long membrane time constants, while neurons in rested flies tend to be electrically silent3. Correlative evidence thus supports the simple view that homeostatic sleep control works by switching sleep-promoting neurons between active and quiescent states3. Here we demonstrate state switching by dFB neurons, identify dopamine as a neuromodulator that operates the switch, and delineate the switching mechanism. Arousing dopamine caused transient hyperpolarization of dFB neurons within tens of milliseconds and lasting excitability suppression within minutes. Both effects were transduced by Dop1R2 receptors and mediated by potassium conductances. The switch to electrical silence involved the downregulation of voltage-gated A-type currents carried by Shaker and Shab, and the upregulation of voltage-independent leak currents through a two-pore-domain potassium channel that we term Sandman. Sandman is encoded by the CG8713 gene and translocates to the plasma membrane in response to dopamine. dFB-restricted interference with the expression of Shaker or Sandman decreased or increased sleep, respectively, by slowing the repetitive discharge of dFB neurons in the ON state or blocking their entry into the OFF state. Biophysical changes in a small population of neurons are thus linked to the control of sleep–wake state.

“Operation of a homeostatic sleep switch” by Diogo Pimentel, Jeffrey M. Donlea, Clifford B. Talbot, Seoho M. Song, Alexander J. F. Thurston and Gero Miesenböck in Nature. Published online August 3 2016 doi:10.1038/nature19055

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