Three groups of scientists working in Switzerland and in France have identified in vitro and studied in detail, for the first time, "sleep-promoting neurons" (nerve cells) located in a tiny area at the base of the brain. Co-ordinated by Prof. Michel Muhlethaler and Dr Mauro Serafin of the University of Geneva, the study showed that the sleep-promoting neurons were clearly different from all surrounding nerve cells, through their triangular shape, particular electrical activity and - most surprisingly - their unusual reactions to certain substances exchanged between nerve cells.

Indeed, neurobiologist Thierry Gallopin discovered that these sleep-promoting neurons, that must be active for sleep to occur, are maintained in an inactive state during wakefulness by the joint effect of three substances: noradrenaline, acetylcholine and serotonin. These usually excitatory substances are produced in the brain by neurons in the so-called "waking systems", in order to promote cerebral activity.

"The sleep-promoting cells and those in the waking systems are able to inhibit each other, that is to influence each other to decrease their electrical activity", says Prof. Muhlethaler. "This is called a reciprocal inhibitory interaction. In everyday life, waking and sleeping phases should depend on an equilibrium being reached between the two types of cells. A person will fall asleep as soon as the sleep neurons become activated and inhibit the neurons in the waking systems."

The research was a collaboration between the University of Geneva and two French laboratories belonging to the INSERM and the CNRS, based respectively in Lyon (group of Dr Patrice Fort and Dr Pierre-Herve Luppi) and in Paris (groupe of Dr Etienne Audinat and Prof. Jean Rossier). This identification of a reciprocal inhibitory mechanism between neurons involved in sleep and wakefulness is clearly a major discovery, as evidenced by the rapid publication of the results in Nature.

As early as 20 years ago, the scientific community had recognized the existence of neurons that are active during sleep and inactive during wakefulness, however their precise localization and function were unknown. Their position was traced to the VLPO (ventro-lateral pre-optic) area of the brain four years ago, by the American scientist Chris Saper's groupe. Two years later, his team went on to discover that the sleep neurons formed projections towards waking systems, where they released an inhibitory neurotransmitter called GABA.

Now, with their in vitro techniques based on rat brain slices, the Swiss and French researchers have not only defined the "personality" of the sleep neurons but have also opened up new possibilities for studying them further. This may in due course lead to understanding why sleep is necessary for survival.
Moreover, the discovery does not yet explain how we are induced to sleep, i.e. what causes the shift in the equilibrium between the two types of neurons. Our body probably experiences two influences that must ultimately affect the sleep neurons. Firstly, the day and night pattern (the sleep neurons lie close to a part of the brain that acts like a clock under the effect of sunlight). Secondly, one or several as yet unknown metabolic factors may be involved. Such a substance might accumulate during the day, to then be eliminated during sleep. Conversely, the unknown substance might be used up during the day, and would have to be created again during sleep. This would explain why fatigue itself tends to build up, and why a particularly long snooze is necessary to compensate for a sleepless night.

A sleep-promoting neuron
Photograph of a sleep-promoting neuron. On the left, one can see the tip of a glass micro-electrode that measures the electrical activity of the cell without damaging it. (Photograph: University of Geneva)

Relaxing under duress!
These three graphs show the electrical activity of a sleep neuron:
1. in its normal state;
2. inhibition under the effect of noradrenaline, acetylcholine and serotonin;
3. returning to its normal state.

Click on one of the pictures in order to get an enlargement

Title of the publication in Nature:
"Identification of sleep-promoting neurons in vitro", Thierry Gallopin, Patrice Fort, Emmanuel Eggermann, Bruno Cauli, Pierre-Herve Luppi, Jean Rossier, Etienne Audinat, Michel Muhlethaler & Mauro Serafin, Nature, April 27, 2000.

For further information, please contact:
Michel Muhlethaler
Département de Physiologie, Centre médical universitaire,
phone +41 78 607 66 74 ou +41 22 702 58 07
fax +41 22 702 54 02