No top-down control for sleep, wakefulness

SPOKANE – Feeling sleepy? That’s because parts of your brain actually are asleep, according to a new theoretical paper by WSU sleep scientists.
Contrary to conventional wisdom, the researchers say, there’s no control center in your brain that dictates when it‘s time for you to drift off to dreamland. Instead, sleep creeps up on you as independent groups of brain cells become fatigued and switch into a sleep state even while you are still (mostly) awake. Eventually, a threshold number of groups switch and you doze off.
 
Making sense
Lead author James Krueger said the view of sleep as an “emergent property” explains familiar experiences that the top-down model doesn’t — such as sleepwalking, in which an unconscious person is able to navigate around objects, and sleep inertia, the sluggishness we feel upon waking in the morning.
“If you explain it in terms of bits and pieces of the brain, instead of a top-down phenomenon, all of a sudden you can make sense of these things,” said Krueger. “The old paradigm doesn’t even address these things.”
Krueger teamed with fellow neurobiologists David Rector, Hans Van Dongen, Gregory Belenky and Jaak Panksepp, and electrical engineer Sandip Roy on the work. Their paper, “Sleep as a fundamental property of neuronal assemblies,” appears in the December issue of Nature Reviews/Neuroscience. It is available ONLINE
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www.nature.com/nrn/journal/vaop/ncurrent/pdf/nrn2521.html.
 
Assimilating research
The authors drew on evidence from several lines of research to develop their hypothesis:
• A group of brain cells that work together to perform a certain function become less responsive and switch into a sleep-like state after the cells have been active for a long time. The likelihood that a given group of cells will enter the sleep state is proportional to how long it has been “awake” and how active it has been — in other words, how hard it has been working.
• While you are awake, the cerebrospinal fluid bathing your brain accumulates proteins called sleep regulatory substances, or SRSs. When the level of SRSs gets high enough, you go to sleep. Putting a drop of an SRS onto a neuronal group causes that group to enter the sleep state, showing that sleep can occur in a group of a few hundred cells without affecting the rest of the brain.
• Co-author Roy developed a mathematical model accounting for the experimental finding that when one neuronal group goes into a sleep-like state, neighboring groups become more likely to do so. The same happens when a sleeping group returns to wakefulness; its communications with its neighbors prompt them to “wake up” as well. The model showed that as communication among groups spreads, it can lead to the global synchronization that causes the whole animal to wake or sleep.
Krueger said such behavior is typical of all sorts of coordinated networks of functional units that operate mostly independently.
“Whether it’s an engineered system or whether it’s fireflies glowing on a summer’s evening, they tend to synchronize,” he said.
 
Centers coordinate
Krueger added that the classic brain “sleep centers” still have a role in the new paradigm. They coordinate the sleep-like and waking-like states of neuronal groups to help the organism adapt to its surroundings (such as whether it’s light or dark out) and achieve peak performance.
The paper’s authors research many major aspects of sleep biology. Krueger studies the biochemistry of sleep; Rector explores the connections between neuronal activity and sleep/wake cycles; Van Dongen and Belenky study the relations between sleep and human performance; Panksepp studies the mechanisms of instinctual emotional and motivational behaviors; and Roy models network formation and coordination of action among independent units.

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