Brain energetics during the sleep–wake cycle
Introduction
Sleep is a universal and evolutionarily conserved behavior shared by species in the animal kingdom regardless of the great diversity of their ecological constraints. Although we do not yet have a fundamental understanding of why animals need to sleep, it is generally accepted that sleep allows the brain to perform critical operations that are largely incompatible with wakefulness [1]. The brain is a constant energy sink, accounting for up to one fifth of total body metabolism. Most of this energy utilization is due to information processing by neuronal-glial networks in the cortical grey matter [2]. The latter is necessary to implement appropriate behavioral responses to the afferent stimuli that are constantly barraging sense organs during wakefulness. Sleep interrupts the connection with the external world, but not the high cerebral metabolic demand. First, brain energy expenditure in non rapid eye movement (NREM) sleep only decreases to ∼85% of the waking value, which is higher than the minimal amount of energy required to sustain consciousness [3••]. Second, rapid eye movement (REM) sleep is as expensive as wakefulness and the suspension of thermoregulation during REM sleep is paradoxically associated with increases in brain metabolic heat production and temperature [4]. Third, neither torpor/hibernation (for instance, in mammals undergoing daily hypothermia) [5] nor several anesthetic states [6] can completely redeem sleep need and recovery, in spite of the loss of consciousness and the accompanying decrease of energy use. Sleep must be related to some essential functions that are adaptive to the organism in the face of their relatively high energy requirements. Here we discuss how the glymphatic and ionostatic functions of the brain contribute to shape the metabolic correlates of sleep and associated neuronal network homeostasis.
Section snippets
Oxidative shift in brain energy metabolism during state transitions
Cerebral energy production is reliant on uptake and metabolism of circulating glucose as well as oxygen diffusing from bloodstream supporting the near-complete oxidation of the sugar. The oxygen–glucose utilization stoichiometry (oxygen–glucose index, OGI) is about 5.1–5.4 in quiet waking conditions (note that 6 mol of oxygen are required to fully oxidize 1 mol of glucose). The excess carbohydrates are processed through aerobic glycolysis, so termed because the pyruvate generated from glucose is
Coupling between aerobic glycolysis and plasticity by norepinephrine
The benefits for adopting the inefficient metabolic strategy of aerobic glycolysis during active waking behavior are presently unknown, but aerobic glycolysis is abolished by noradrenergic blockade, suggesting that it is related to the processing of sensory information [reviewed by 7]. Indeed, responsiveness to and discrimination between meaningful and meaningless environmental stimuli hinges on the activation of wake-promoting systems. During NREM sleep, firing of cholinergic and noradrenergic
State–dependent astrocyte–neuron functional and metabolic interactions
The transition from wakefulness to sleep is accompanied by a marked expansion of extracellular space [49, 53] as well as rapid and sustained decrease in extracellular K+ and increase in extracellular Ca2+ and Mg2+ [54••]. These changes in interstitial fluid volume and ionic composition are reversed during the transition from sleep to wakefulness and are largely dependent on neuromodulators, while they survive suppression of neuronal firing [49, 54••]. As wake-promoting neuromodulators generally
Network homeostasis as an energy–consuming facet of sleep
Sleep is an adaptive behavior that increases fitness and behavioral performance, as evidenced by the dramatic adverse effects of sleep deprivation, including reduced alertness and ability to acquire and store information [1]. Adaptation to the environment, a crucial factor impacting on the probability of survival, entails the capacity to modify behavior to mutating conditions. Refinement of neuronal circuits occur in an experience-dependent manner, whereby synapses constantly undergo Hebbian
Conclusions
The varying degree of aerobic glycolysis between sleep and wakefulness likely reflects the altered astrocytic participation in neuronal activity and the ensuing changes in synaptic plasticity brought about by differences in neuromodulatory tone. During sleep, selective homeostatic changes are obtained by exposing synapses to neuronal discharge patterns that are energy demanding. Overall, both in terms of energy metabolism and neuronal activity, the immediate sleep ‘savings’ are quantitatively
Funding
This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 701635. The content is solely the responsibility of the authors and does not necessarily represent the official views of the European Union.
Conflict of interest statement
Nothing declared.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
References (86)
- et al.
Synaptic energy use and supply
Neuron
(2012) - et al.
The minimal energetic requirement of sustained awareness after brain injury
Curr Biol
(2016) - et al.
Different effects of sleep deprivation and torpor on EEG slow-wave characteristics in Djungarian hamsters
Cereb Cortex
(2017) - et al.
Sleep and brain energy levels: ATP changes during sleep
J Neurosci
(2010) - et al.
Study of regional cerebral glucose metabolism, in man, while awake or asleep, by positron emission tomography
Rev Electroencephalogr Neurophysiol Clin
(1987) - et al.
Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography
Life Sci
(1989) - et al.
Dynamic features of hemodynamic and metabolic changes in the human brain during all-night sleep as revealed by near-infrared spectroscopy
Brain Res
(1994) - et al.
The effects of sleep and lack of sleep on the cerebral circulation and metabolism of normal young men
J Clin Invest
(1955) - et al.
Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2)
Brain Res
(1991) - et al.
Sleep slow-wave activity regulates cerebral glycolytic metabolism
Cereb Cortex
(2013)
Regional aerobic glycolysis in the human brain
Proc Natl Acad Sci U S A
Brain aerobic glycolysis and motor adaptation learning
Proc Natl Acad Sci U S A
Learning-induced gene expression in the hippocampus reveals a role of neuron–astrocyte metabolic coupling in long term memory
PLoS One
Differential expression of plasticity-related genes in waking and sleep and their regulation by the noradrenergic system
J Neurosci
Cortical firing and sleep homeostasis
Neuron
Glycolysis and glutamate accumulation into synaptic vesicles. Role of glyceraldehyde phosphate dehydrogenase and 3-phosphoglycerate kinase
J Biol Chem
Synaptic vesicle-bound pyruvate kinase can support vesicular glutamate uptake
Neurochem Res
Requirement of glycogenolysis for uptake of increased extracellular K(+) in astrocytes: potential implications for K(+) homeostasis and glycogen usage in brain
Neurochem Res
Fast and reversible stimulation of astrocytic glycolysis by K+ and a delayed and persistent effect of glutamate
J Neurosci
Does global astrocytic calcium signaling participate in awake brain state transitions and neuronal circuit function?
Neurochem Res
Sleep, recovery, and metaregulation: explaining the benefits of sleep
Nat Sci Sleep
A brain-warming function for REM sleep
Neurosci Biobehav Rev
Rapid eye movement sleep debt accrues in mice exposed to volatile anesthetics
Anesthesiology
Aerobic glycolysis during brain activation: adrenergic regulation and influence of norepinephrine on astrocytic metabolism
J Neurochem
Effect of sleep on brain labile phosphates and metabolic rate
Am J Physiol
Brain extracellular glucose assessed by voltammetry throughout the rat sleep–wake cycle
Eur J Neurosci
Sleep/wake dependent changes in cortical glucose concentrations
J Neurochem
Lactate as a biomarker for sleep
Sleep
Simultaneous electroencephalography, real-time measurement of lactate concentration and optogenetic manipulation of neuronal activity in the rodent cerebral cortex
J Vis Exp
Lactate in the brain of the freely moving rat: voltammetric monitoring of the changes related to the sleep–wake states
Eur J Neurosci
Cerebral lactate dynamics across sleep/wake cycles
Front Comput Neurosci
Extracellular levels of lactate, but not oxygen, reflect sleep homeostasis in the rat cerebral cortex
Sleep
Brain metabolism in emotional excitement and in sleep
Am J Physiol
Glucose and lactate monitoring across the rat sleep–wake cycle
Decreases in rat extracellular hippocampal glucose concentration associated with cognitive demand during a spatial task
Proc Natl Acad Sci U S A
Simultaneous real-time measurement of EEG/EMG and l-glutamate in mice: a biosensor study of neuronal activity during sleep
J Electroanal Chem (Lausanne)
Long-term homeostasis of extracellular glutamate in the rat cerebral cortex across sleep and waking states
J Neurosci
What is the meaning of the ATP surge during sleep?
Sleep
Nonoxidative glucose consumption during focal physiologic neural activity
Science
Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects
Proc Natl Acad Sci U S A
Regional cerebral oxidative and total glucose consumption during rest and activation studied with positron emission tomography
Acta Physiol Scand
Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation: evidence obtained with the Kety-Schmidt technique
J Cereb Blood Flow Metab
Cerebral glucose utilization during sleep–wake cycle in man determined by positron emission tomography and [18F]2-fluoro-2-deoxy-d-glucose method
Brain Res
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