The closed eyes, the unresponsiveness, the drool — sleep is an easily recognizable, all-encompassing state. But the divide between sleep and wakefulness may not be as clearcut as we thought.

Research published today inNature demonstrates that in visibly awake rats, neurons in some areas of the brain’s cortex briefly go ‘offline’. In these pockets, neuronal patterns resemble those associated with non-rapid eye movement (NREM) sleep1.

“The rats were awake, but awake with a nice sprinkling of localized sleep in the cortex,” says Guilio Tononi, a neuroscientist at the University of Wisconsin–Madison and lead author of the study.

The team used different techniques to measure both the local and global electric field potentials in the brain. Localized neural activity was measured using microwire arrays implanted deep in the frontal and parietal cortex field, whereas electroencephalography (EEG) detects global neuronal activity such as slow waves seen in NREM sleep. During slow-wave activity, neurons oscillate between ON and OFF states, but are typically OFF.

By recording the activity of many small populations of neurons, Tononi and his colleagues showed that OFF states occur randomly throughout the cortex when a rat has been awake for a long time. “If we could watch the whole brain, it would be like watching boiling water – when you are awake, just before boiling, all the neurons are ON. As the animal gets tired, the OFF periods would then be the bubbles; where they appear is impossible to predict,” he says.

Slow waves were thought to be absent during normal waking behaviour, but the new study emphasizes that slow-wave activity can be very localized, says David McCormick, a neurobiologist at Yale University in New Haven, Connecticut. “Call it a cortical blink — just a brief shutdown of a piece of cortex that can disrupt neural processing.”

Napping neurons

The napping neurons can affect behaviour. The number of OFF periods grew as the length of time the animal had been kept awake rose, impairing its cognitive performance when challenged with a difficult task — reaching for a sugar pellet through a slot in their plexiglass cage.

Toroni notes that compared to the global phenomenon we recognize as sleep, the presence of localized OFF neurons “is more insidious because we can’t tell it’s happening”. In humans, this could explain why sleep deprivation can impair judgment.

Interestingly, earlier this month Tononi and colleagues reported that, even during ‘global’ sleep, slow waves are localized and occur in specific regions2. They recorded the EEG and localized neuronal activity using deep electrodes in a number of brain regions in people undergoing brain surgery and found that the slow waves can propagate from the prefrontal cortex to the temporal lobe to the hippocampus. “Even in sleep, the slow waves were more local than expected,” says Tononi.

Together, these findings suggest that scientists may have had an overly simplistic idea of waking and sleep states. “If these both happen — local sleep during waking and local waking during sleep — then it may lead to a rethinking of our concepts of sleep states,” says Peter Achermann, a sleep researcher at the University of Zurich in Switzerland.

Redefining opposites



“This paper clearly confirms the suspicion that sleep can occur in parts of the brain when the rest of the brain is awake — that’s what we see in the clinic,” says Mark Mahowald, director of the Minnesota Regional Sleep Disorders Center in Minneapolis. Sleep-walking is the best example of how such simultaneous mixtures of wakefulness and sleep can result in complex behaviours, he adds.

Tononi agrees. “Our work doesn’t redefine sleep — we have a good definition based on behavioural aspects — but it does suggest that the definition may not be sufficient to describe disassociated states.”

This work may help to pin down a better understanding of the function of sleep — a long-term goal of Tononi’s research group. “We suspect sleep has something to do with synapses because we find a net strengthening of synapses during sleep,” he says. Sleep seems to be a time of recalibrating synaptic activity in the brain, so he wants to determine whether napping neurons in an awake brain are protective, restorative or just plain harmful.



Jegarakshagan R. Gokul


Jegarakshagan Gokul

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