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Scientists Discover Key Neural Pathways that Allow Transition to Sleep

New research sheds light on the neural mechanisms that allow us to transition from wakefulness to sleep and back again.
Image: Flickr/Mike Burns

For something that happens as regularly as falling asleep, neuroscientists know remarkably little about how it works. One minute you're awake and the next minute you're flying through the city fighting a giant lizard that vaguely resembles your mother, but how you got there was always something of a mystery. Yet thanks to new research coming out of the University of Maryland School of Medicine, scientists were able to identify the key neural mechanisms regulating our transitions between wakefulness and sleep, shedding some light on this elusive phenomenon.

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As the Maryland team detailed in a recent paper in Nature Communications, in order to determine the neural process regulating transitions between sleep and wakefulness, it focused on the suprachiasmatic nucleus in the hypothalamus, a small group of brain cells long known to be responsible for regulating the body's circadian cycles. These cycles refer to the physiological or behavioral changes in a plant or animal that occur in roughly 24-hour cycles. Circadian rhythms are primarily modulated by the day-night cycle, and inform an organism when to do things like eat, sleep, or migrate, as the case may be.

The Maryland team examined a group of neuronal ion channels (proteins which allow ions, or electrically charged atoms, to move across a cell), known as BK potassium channels, within the suprachiasmatic nuclei of a number of mice. These BK potassium channels are particularly active in the suprachiasmatic nucleus, and in mice, which have sleep schedules opposite of humans, these channels are most active at night while the mice are awake.

According to Andrea Meredith, a Maryland professor of Physiology who led the study, during the day these BK channels were inactive and inhibited wakefulness in the mice. She and her colleagues were able to determine this by comparing a group of regular mice with a group of mice which had been genetically altered so that their BK channels wouldn't become inactive during the day. To Meredith's surprise, the genetically altered mice that were incapable of deactivating their BK channels exhibited more wakefulness during the day.

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Image via Andrea Meredith, et al.

Scientists have previously linked BK potassium channels with a number of other physiological processes such as activating muscles and controlling blood pressure, as well as playing a role in motor control and memory in the brain. But the Maryland team's study was the first to link it to the regulation of circadian rhythms, shedding some critical light on the mysterious transition between sleep and wakefulness.

"We knew that BK channels were widely important throughout the body," said Meredith. "But now we have strong evidence that they are specifically and intrinsically involved in the wake-sleep cycle. That's really exciting."

Prior to the Maryland team's work, scientists thought that the patterns of neuronal firing in the suprachiasmatic nucleus were regulated by the number of BK potassium channels existing on the surface of suprachiasmatic nucleus neurons. Yet according to Meredith and her colleagues, their new work shows that this previous model is too simplistic. The day/night pattern of neuron firings in the suprachiasmatic nucleus is not reliant on the number of BK channels, but rather the fact that these channels are active or inactive at specific times each day.

According to the team, its discovery could have far reaching clinical applications, particularly for those with sleep disorders such as jet lag, seasonal affective disorder, and other disorders which mess with the suprachiasmatic nucleus' circadian clock. If those suffering from a particular sleep disorder are having trouble falling asleep, the medicine could activate the BK channels as needed.