Gero Miesenböck

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. Perhaps the only opportunity for separating causation from correlation exists in spacialist 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 strands of evidence have begun to converge on the idea that sleep-control neurons estimate the need for sleep by monitoring the leakage of electrons from the transport chains of their mitochondria. Univalent reductions of O2 lead to the production of superoxide and hydrogen peroxide, lipid peroxidation, and mitochondrial fission. Sleep, like aging, may be an inescapable consequence of aerobic metabolism.