The Electron Leak Hypothesis of Sleep

Host

Ibrahim Taştekin, PhD, Behavior and Metabolism Lab

Venue

Seminar room

Abstract

Sleep pressure, the process variable in sleep homeostasis, has lacked a physical interpretation. Although prolonged waking leads to numerous changes in the brain, it remains generally indeterminable whether these changes are causes or consequences of a growing need for sleep. The only opportunity for separating causation from correlation exists in neurons with active roles in the induction and maintenance of sleep; in these cells, sleep’s proximate (and maybe also its ultimate) causes must interlock directly with the processes that regulate spiking. Several lines of evidence have begun to converge on the idea that sleep-control neurons gear their electrical discharge to the leakage of electrons from the mitochondrial transport chain. Sleep loss creates an imbalance between electron supply and ATP demand that diverts electrons into uncontrolled side reactions with molecular oxygen, producing reactive oxygen species which fragment membrane lipids. Sleep-inducing neurons count the release of lipid breakdown products (and transduce this signal into sleep) in a process that involves an allosteric dialogue between a voltage-gated potassium channel and its redox-sensitive β-subunit. Sleep, like aging, may thus be an inescapable consequence of aerobic metabolism.

Bio

Gero Miesenböck is Waynflete Professor of Physiology and founding Director of the Centre for Neural Circuits and Behaviour at the University of Oxford. Before coming to Oxford in 2007, he held faculty appointments at Memorial Sloan-Kettering Cancer Center and Yale University. Gero has received many awards for the invention of optogenetics, including the Brain Prize, the Shaw Prize, the Lousia Gross Horwitz Prize, and the Japan Prize. He is a member of the US, Austrian, and German National Academies of Sciences and a Fellow of the Royal Society.

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Champalimaud Research (CR) Colloquia Series is a seminar programme organised by the Champalimaud Centre for the Unknown to promote the discussion about the most interesting and significant questions in neuroscience and physiology & cancer with appointed speakers by the CR Community.