, 2012) Finally, the question of the heritability of stress resi

, 2012). Finally, the question of the heritability of stress resilience and susceptibility is particularly fascinating and represents another important challenge that will need to be addressed in the future. We thank

Dr. Johannes Bohacek for critical reading of the check details manuscript and Rreze Gecaj for initial figures for this review. The lab of I.M.M. is funded by the University Zürich, the Swiss Federal Institute of Technology, The Swiss National Foundation, the National Center of Competence in Research “Neural Plasticity and Repair,” SystemsX, Roche. T.B.F. is funded by the Swiss National Science Foundation. “
“The nervous system consumes a disproportionate fraction of the resting body’s energy production: in humans the brain is only 2% of the body’s mass, yet it uses ∼20% of the O2 consumed by the resting body (Mink et al., 1981), while the retina alone uses 10% of the fly’s resting ATP consumption (Laughlin et al., 1998). The relative

energy consumption of the brain has increased particularly during the evolution of humans from lower primates (Mink et al., 1981; Aiello and Wheeler, 1995), reflecting a 3-fold expansion in the size of the brain relative to the body and an increase in the number of synapses per cortical neuron (Abeles, 1991). This greater energy allocation to CNS tissue over millions of years underpins our brains’ greater cognitive powers, and was made possible by an increased click here and higher-quality food intake, along with less energy expenditure on the gut and locomotion (Aiello and Wheeler, 1995; Navarrete et al., 2011). What is all this energy used for very in the brain, how does it determine the brain’s information processing power, and how does the brain’s high energy use predispose it to problems when energy is not supplied at the necessary rate? We will review how most brain energy is used on synapses, investigate how pre- and postsynaptic terminals are optimized to maximize information transmission at minimum energy

cost, and assess how ATP provision to synapses is regulated to satisfy their energetic needs. We then consider how synapse energy use changes with development and synaptic plasticity, and between wake and sleep states, before relating how defects in synaptic energy supply can lead to disease. The ATP consumption by the major subcellular processes underlying signaling in the brain (Figure 1) has been estimated for rat cerebral cortex (Attwell and Laughlin, 2001) and for human cortex (Lennie, 2003). Anatomical data on mean cell size, and the capacitance per area of membrane, were used to estimate the Na+ that enters to produce action potentials and thus needs to be pumped out again by the Na+/K+-ATPase, consuming ATP.

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