M any brain centers are involved in keeping us awake. One example is the recently discovered hypocretin system located in the posterior hypothalamus. In this issue of the JCI, Rao et al. show that, in mice, synapses targeting hypocretin neurons become stronger when wakefulness is prolonged beyond its physiological duration (see the related article beginning on page 4022). This increase in synaptic strength may be one of the mechanisms that help us to stay awake when we are sleep deprived, but it may also represent one of the signals telling the brain that it is time to sleep.