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Brain Stronger During Waking Hours, Weaker During Sleep

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Most people know it from experience: After so many hours of being awake, your brain feels unable to absorb any more–and several hours of sleep will refresh it.

Now new research clarifies this phenomenon, supporting the idea that sleep plays a critical role in brain’s ability to change in response to its environment. This ability, called plasticity, is at the heart of learning.

The UW-Madison scientists showed by several measures that synapses — nerve cell connections central to brain plasticity — were very strong when mice had been awake and weak when they had been asleep.

The new findings reinforce the UW-Madison researchers’ highly-debated hypothesis about the role of sleep. They believe that people sleep so that their synapses can downsize and prepare for a new day and the next round of learning and synaptic strengthening.

The human brain expends up to 80 percent of its energy on synaptic activity, constantly adding and strengthening connections in response to all kinds of stimulation, explains study author Chiara Cirelli, associate professor of psychiatry.

Given that each of the millions of neurons in the human brain contains thousands of synapses, this energy expenditure “is huge and can’t be sustained.”

“We need an off-line period, when we are not exposed to the environment, to take synapses down,” Cirelli say. “We believe that’s why humans and all living organisms sleep. Without sleep, the brain reaches a saturation point that taxes its energy budget, its store of supplies and its ability to learn further.”

To test the theory, researchers conducted both molecular and electro-physiological studies in rats to evaluate synaptic potentiation, or strengthening, and depression, or weakening, following sleeping and waking times. In one set of experiments, they looked at brain slices to measure the number of specific receptors, or binding sites, that had moved to synapses.

“Recent research has shown that as synaptic activity increases, more of these glutamatergic receptors enter the synapse and make it bigger and stronger,” explains Cirelli.

The Wisconsin group was surprised to find that rats had an almost 50 percent receptor increase after a period of wakefulness compared to rats that had been asleep.

In a second molecular experiment, the scientists examined how many of the receptors underwent phosphorylation, another indicator of synaptic potentiation. They found phosphorylation levels were much higher during waking than sleeping. The results were the same when they measured other enzymes that are typically active during synaptic potentiation.

To strengthen their case, Cirelli and colleagues also performed studies in live rats to evaluate electrical signals reflecting synaptic changes at different times. This involved stimulating one side of each rat’s brain with an electrode following waking and sleeping and then measuring the “evoked response,” which is similar to an EEG, on another side.

The studies again showed that, for the same levels of stimulation, responses were stronger following a long period of waking and weaker after sleep, suggesting that synapses must have grown stronger.

“Taken together, these molecular and electro-physiological measures fit nicely with the idea that our brain circuits get progressively stronger during wakefulness and that sleep helps to recalibrate them to a sustainable baseline,” says Cirelli.

The theory she and collaborator Dr. Giulio Tononi, professor of psychiatry, have developed, called the synaptic homeostasis hypothesis, runs against the grain of what many scientists currently think about how sleep affects learning. The most popular notion these days, says Cirelli, is that during sleep synapses are hard at work replaying the information acquired during the previous waking hours, consolidating that information by becoming even stronger.

“That’s different from what we think,” she says. “We believe that learning occurs only when we are awake, and sleep’s main function is to keep our brains and all its synapses lean and efficient.”

Brain Research Bulletin

doi:10.1016/j.brainresbull.2007.10.040 

Research report

Cortical metabolic rates as measured by 2-deoxyglucose-uptake are increased after waking and decreased after sleep in mice

V.V. Vyazovskiya, b, C. Cirellinext termb, G. Tononib, Corresponding Author Contact Information, E-mail The Corresponding Author and I. Toblera, Corresponding Author Contact Information, E-mail The Corresponding Author
aInstitute of Pharmacology and Toxicology, University of Zurich, Winterthurerstr. 190, CH-8057 Zürich, Switzerland
bDepartment of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Boulevard, Madison, WI 53719, USA
Received 10 August 2007;  revised 11 October 2007;  accepted 12 October 2007.  Available online 20 November 2007.

Abstract

A recent hypothesis suggests that a major function of sleep is to renormalize previous termsynapticnext term changes that occur during wakefulness as a result of learning processes [G. Tononi, C. Cirelli, Sleep and previous termsynaptic homeostasis:next term a hypothesis, Brain Res. Bull. 62 (2003) 143–150; G. Tononi, C. Cirelli, Sleep function and previous termsynaptic homeostasis,next term Sleep Med. Rev. 10 (2006) 49–62]. Specifically, according to this previous termsynaptic homeostasisnext term hypothesis, wakefulness results in a net increase in previous termsynapticnext termprevious termsynapticnext term downscaling. Since previous termsynapticnext term activity accounts for a large fraction of brain energy metabolism, one of the predictions of the hypothesis is that if previous termsynapticnext term weight increases in the course of wakefulness, cerebral metabolic rates should also increase, while the opposite would happen after a period of sleep. In this study we therefore measured brain metabolic rate during wakefulness and determined whether it was affected by the previous sleep–wake history. Three groups of mice in which behavioral states were determined by visual observation were subjected to 6 h of sleep deprivation (SD). Group 1 was injected with 2-deoxyglucose (2-DG) 45 min before the end of SD, while Group 2 and Group 3 were injected with 2-DG after an additional period (2–3 h) of waking or sleep, respectively. During the 45-min interval between 2-DG injection and sacrifice all mice were kept awake. We found that in mice that slept not, vert, similar2.5 h the 2-DG-uptake was globally decreased, on average by 15–20%, compared to the first two groups that were kept awake. On average, Group 2, which stayed awake not, vert, similar2 h more than Group 1, showed only a small further increase in 2-DG-uptake relative to Group 1. Moreover, the brain regions in which 2-DG-uptake increased the least when waking was prolonged by not, vert, similar2 h showed the most pronounced decrease in DG-uptake after sleep. The data are consistent with the prediction that sleep may reset cerebral metabolic rates to a lower level. strength, while sleep is associated with


Keywords: Sleep regulation; Sleep previous termhomeostasis; Synaptic homeostasisnext term; Deoxyglucose; Mice; Brain metabolism

Abbreviations: 2-DG, 2-deoxyglucose; Cg, cingulate cortex; CC, corpus callosum; RSG, retrosplenial granular cortex; Cpu, caudate putamen; EEG, electroencephalogram; EMG, electromyogram; FD, food deprivation; GAD, glutamate decarboxylase; NREM sleep, non-rapid eye movement sleep; PB, Probst bundle; PET, positron emission tomography; REM sleep, rapid eye movement sleep; SEM, standard error of the mean; SD, sleep deprivation; SWA, slow wave activity

Written by huehueteotl

January 21, 2008 at 2:34 pm

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