Elsevier

Current Opinion in Neurobiology

Volume 47, December 2017, Pages 65-72
Current Opinion in Neurobiology

Brain energetics during the sleep–wake cycle

https://doi.org/10.1016/j.conb.2017.09.010Get rights and content

Highlights

  • Cerebral aerobic glycolysis and lactate levels are elevated during wakefulness.

  • Sleep is metabolically expensive and increases oxygen–glucose utilization stoichiometry.

  • Noradrenergic tone targets brain ionostatic, glymphatic and metabolic functions.

  • Astrocytes affect state-specific presynaptic/postsynaptic neuronal activity and plasticity.

Brain activity during wakefulness is associated with high metabolic rates that are believed to support information processing and memory encoding. In spite of loss of consciousness, sleep still carries a substantial energy cost. Experimental evidence supports a cerebral metabolic shift taking place during sleep that suppresses aerobic glycolysis, a hallmark of environment-oriented waking behavior and synaptic plasticity. Recent studies reveal that glial astrocytes respond to the reduction of wake-promoting neuromodulators by regulating volume, composition and glymphatic drainage of interstitial fluid. These events are accompanied by changes in neuronal discharge patterns, astrocyte–neuron interactions, synaptic transactions and underlying metabolic features. Internally-generated neuronal activity and network homeostasis are proposed to account for the high sleep-related energy demand.

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

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