A ‘cocktail’ in the brain can trigger sleep

Waking and falling asleep do not happen the way researchers had thought they did, a new study suggests. Its results could affect how scientists understand sleep and awareness.

Neurons are the cells that power brain activity. Researchers thought that these cells decided when to switch the brain from sleep to wakefulness — and back again. However, these cells aren’t the brain’s only sandmen or roosters, the new study suggests. Certain chemicals help set the pace of neuron activity. And the new research indicates they can directly wake the brain or lull it to sleep. They do this by changing the concentration of certain ions in the brain. (Ions are atoms or groups of atoms that have an electric charge.)

The researchers described their new findings April 29 in Science.

Scientists knew that levels of potassium ions, calcium ions and magnesium ions in the brain change during sleep or wakefulness. But they had never shown a direct link between those ions and sleep or wakefulness. That’s because those scientists had been focused mostly on what the neurons were doing, says study leader Maiken Nedergaard. She works for the University of Rochester in New York. As a neuroscientist, she studies the structure and functions of the brain. She got interested in sleep after her lab found a plumbing system that washes wastes out of the brain during sleep.

While studying that plumbing system, Nedergaard observed that levels of potassium ions are high when mice are awake. Potassium levels fall during sleep. Calcium and magnesium ions do the opposite. They peak during sleep and fall when mice are awake. (The same thing probably happens in people.)

In their new study, the researchers put a “cocktail” of wake chemicals into mouse brains. The chemicals are known as neuromodulators. That term refers to the fact that they change — or modulate — the activity of neurons.

After the treatment, the levels of potassium ions floating between brain cells shot up. That change happened even when the researchers gave the mice another chemical to stop neuron activity.

These data suggest that the brain chemicals directly affect ion levels with no help from the cells themselves. Exactly how neuromodulators do this still is not known.

Similar changes happened when mice were put to sleep with knock-out drugs that anesthetized (Uh-NESS-thuh-tized) them. When wide-awake mice were given these drugs, levels of potassium ions in their brains fell sharply. At the same time, levels of calcium ions and magnesium ions rose.

As knocked-out mice awoke, their potassium-ion levels rose quickly. But calcium and magnesium levels dropped slowly. As a result, the mice “are totally confused,” says Nedergaard. “They bump into their cages, they run around and they don’t know what they are doing.”

Those results may help explain why people are groggy after waking up from anesthesia. Their potassium ions are telling them to wake up. But their levels of calcium ions and magnesium ions are still in sleep mode, says Amita Sehgal. She’s a sleep researcher at the University of Pennsylvania School of Medicine in Philadelphia.

Nedergaard says learning more about how ions affect wakefulness and sleep may lead to better understanding of sleep, consciousness and coma. (Coma is a state of unconsciousness, in which a person cannot be wakened.)

Still, practical uses for the work, such as improved sleep drugs, are probably far in the future, says Chiara Cirelli. She’s a neuroscientist at the University of Wisconsin‒Madison. “How they make use of it will take some time,” she says. “But just knowing this is certainly very eye-opening.”

Power Words

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anesthesia     A medicine used to control pain, usually by seeming to put someone asleep. The drug helps to control an individual’s breathing, blood pressure, blood flow and heart rate (and rhythm). It will relax patients, leaving them sleepy. Eventually, they will usually become unconscious. Some “local” anesthetics, however, just numb tissues around where the drug had been applied. In these cases, the patient will remain awake.

anesthetize   To give a substance (usually a drug) that causes a person or animal to temporarily lose the ability to feel pain. Substances that anesthetize are called anesthetics.

calcium   A chemical element which is common in minerals of the Earth’s crust and in sea salt. It is also found in bone mineral and teeth, and can play a role in the movement of certain substances into and out of cells.

coma   A state of deep unconsciousness from which a person cannot be awakened. It usually results from disease or injury.

concentration   (in chemistry) A measurement of how much of one substance has been dissolved into another.

conscious    Aware of and responding to one’s surroundings.

ion   An atom or molecule with an electric charge due to the loss or gain of one or more electrons.

magnesium   A metallic element that is number 12 on the periodic table. It burns with a white light and is the eighth most abundant element in the Earth’s crust.

neuron   The impulse-conducting cells that make up the brain, spinal column and nervous system.

neuromodulator    A chemical in the brain that alters the activity of neurons (nerve cells). Examples of neuromodulators include dopamine and acetylcholine.

neuroscience   Science that deals with the structure or function of the brain and other parts of the nervous system. Researchers in this field are known as neuroscientists.

potassium   A chemical element that occurs as a soft, silver-colored metal. Highly reactive, it burns on contact with air or water with a violet flame. It is found in ocean water, as part of sea salt, and is also found in many minerals.