Abstract

Energy use limits the information processing power of the brain. However, apart from the ATP used to power electrical signalling, a significant fraction of the brain's energy consumption is not directly related to information processing. The brain spends just under half of its energy on non-signalling processes, but it remains poorly understood which tasks are so energetically costly for the brain. We review existing experimental data on subcellular processes that may contribute to this non-signalling energy use, and provide modelling estimates, to try to assess the magnitude of their ATP consumption and consider how their changes in pathology may compromise neuronal function. As a main result, surprisingly little consensus exists on the energetic cost of actin treadmilling, with estimates ranging from < 1% of the brain's global energy budget up to one-half of neuronal energy use. Microtubule treadmilling and protein synthesis have been estimated to account for very small fractions of the brain's energy budget, whereas there is stronger evidence that lipid synthesis and mitochondrial proton leak are energetically expensive. Substantial further research is necessary to close these gaps in knowledge about the brain's energy-expensive non-signalling tasks.

Highlights

  • The human brain is only 2% of the body’s mass but uses 20% of its resting energy production (Kety, 1957; Sokoloff, 1960; Rolfe & Brown, 1997)

  • Theoretical energy budgets for the brain, based on experimental measurements, have established that this disproportionate energy use largely reflects the energetic cost in neurons of pumping out sodium ions that enter to generate synaptic and action potentials (Attwell & Laughlin, 2001; Lennie, 2003; Harris & Attwell, 2012)

  • In a seminal in vivo study on dogs, Astrup et al (1981a) quantified the energy used on the sodium-potassium pump more precisely

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Summary

Introduction

The human brain is only 2% of the body’s mass but uses 20% of its resting energy production (Kety, 1957; Sokoloff, 1960; Rolfe & Brown, 1997). These results demonstrate that a high percentage of ATP use is spent on signalling-related processes such as reversing sodium entry after action potentials, synaptic ion fluxes, and maintaining the resting membrane potential.

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