Neuronal computation is energetically expensive. Consequently, the brain's limited energy supply imposes constraints on its information processing capability. Most brain energy is used on synaptic transmission, making it important to understand how energy is provided to and used by synapses. We describe how information transmission through presynaptic terminals and postsynaptic spines is related to their energy consumption, assess which mechanisms normally ensure an adequate supply of ATP to these structures, consider the influence of synaptic plasticity and changing brain state on synaptic energy use, and explain how disruption of the energy supply to synapses leads to neuropathology. Neuronal computation is energetically expensive and most brain energy is used on synaptic transmission. Here, Harris et al. review how energy is used and regulated at synapses, how its use changes in development, synaptic plasticity, and between wake/sleep states, and the role of synaptic energy supply in disease.
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