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Multiple organs orchestrate the maintenance of proper physiological function in organisms throughout their lifetimes. Recent studies have uncovered that aging and longevity are regulated by cell non-autonomous signaling mechanisms in several organisms. In the brain, particularly in the hypothalamus, aging and longevity are regulated by such cell non-autonomous signaling mechanisms. Several hypothalamic neurons have been identified as regulators of mammalian longevity, and manipulating them promotes lifespan extension or shortens the lifespan in rodent models. The hypothalamic structure and function are evolutionally highly conserved across species. Thus, elucidation of hypothalamic function during the aging process will shed some light on the mechanisms of aging and longevity and, thereby benefiting to human health. Keywords: Cell non-autonomous, Aging, Longevity, Hypothalamus, Sleep, Cross-species comparison, Author(s): Takuya Urushihata[sup.1,2] and Akiko Satoh[sup.1,2] Background Many studies have shown that longevity is regulated through cell non-autonomous signaling mechanisms by pathways originating in central nervous system neurons [1, 2]. [...]

During sleep, most animal species enter a state of reduced consciousness characterized by a marked sensory disconnect. Yet some processing of the external world must remain intact, given that a sleeping animal can be awoken by intense stimuli (for example, a loud noise or a bright light) or by soft but qualitatively salient stimuli (for example, the sound of a baby cooing or hearing one's own name.sup.1-3). How does a sleeping brain retain the ability to process the quality of sensory information? Here we present a paradigm to study the functional underpinnings of sensory discrimination during sleep in Drosophila melanogaster. We show that sleeping vinegar flies, like humans, discern the quality of sensory stimuli and are more likely to wake up in response to salient stimuli. We also show that the salience of a stimulus during sleep can be modulated by internal states. We offer a prototypical blueprint detailing a circuit involved in this process and its modulation as evidence that the system can be used to explore the cellular underpinnings of how a sleeping brain experiences the world. The authors develop a paradigm to study sensory discrimination during sleep in Drosophila melanogaster., Author(s): Alice S. French [sup.1] , Quentin Geissmann [sup.2] , Esteban J. Beckwith [sup.3] , Giorgio F. Gilestro [sup.1] Author Affiliations: (1) Department of Life Sciences, Imperial College London, London, [...]

Author(s): Anissa Kempf [sup.1] , Seoho M. Song [sup.1] , Clifford B. Talbot [sup.1] , Gero Miesenböck [sup.1] Author Affiliations: (1) Centre for Neural Circuits and Behaviour, University of Oxford, [...], The essential but enigmatic functions of sleep.sup.1,2 must be reflected in molecular changes sensed by the brain's sleep-control systems. In the fruitfly Drosophila, about two dozen sleep-inducing neurons.sup.3 with projections to the dorsal fan-shaped body (dFB) adjust their electrical output to sleep need.sup.4, via the antagonistic regulation of two potassium conductances: the leak channel Sandman imposes silence during waking, whereas increased A-type currents through Shaker support tonic firing during sleep.sup.5. Here we show that oxidative byproducts of mitochondrial electron transport.sup.6,7 regulate the activity of dFB neurons through a nicotinamide adenine dinucleotide phosphate (NADPH) cofactor bound to the oxidoreductase domain.sup.8,9 of Shaker's K.sub.V[beta] subunit, Hyperkinetic.sup.10,11. Sleep loss elevates mitochondrial reactive oxygen species in dFB neurons, which register this rise by converting Hyperkinetic to the NADP.sup.+-bound form. The oxidation of the cofactor slows the inactivation of the A-type current and boosts the frequency of action potentials, thereby promoting sleep. Energy metabolism, oxidative stress, and sleep--three processes implicated independently in lifespan, ageing, and degenerative disease.sup.6,12-14--are thus mechanistically connected. K.sub.V[beta] substrates.sup.8,15,16 or inhibitors that alter the ratio of bound NADPH to NADP.sup.+ (and hence the record of sleep debt or waking time) represent prototypes of potential sleep-regulatory drugs. Sleep deprivation in Drosophila elevates reactive oxygen species in sleep-promoting neurons, leading to changes in potassium currents and spiking activity and thereby connecting energy metabolism, oxidative stress, and sleep.

Author(s): Zhiqiang Wang [sup.1] , Jing Ma [sup.1] , Chika Miyoshi [sup.1] , Yuxin Li [sup.2] , Makito Sato [sup.1] , Yukino Ogawa [sup.1] , Tingting Lou [sup.1] , Chengyuan [...], Sleep and wake have global effects on brain physiology, from molecular changes.sup.1-4 and neuronal activities to synaptic plasticity.sup.3-7. Sleep-wake homeostasis is maintained by the generation of a sleep need that accumulates during waking and dissipates during sleep.sup.8-11. Here we investigate the molecular basis of sleep need using quantitative phosphoproteomic analysis of the sleep-deprived and Sleepy mouse models of increased sleep need. Sleep deprivation induces cumulative phosphorylation of the brain proteome, which dissipates during sleep. Sleepy mice, owing to a gain-of-function mutation in the Sik3 gene.sup.12, have a constitutively high sleep need despite increased sleep amount. The brain proteome of these mice exhibits hyperphosphorylation, similar to that seen in the brain of sleep-deprived mice. Comparison of the two models identifies 80 mostly synaptic sleep-need-index phosphoproteins (SNIPPs), in which phosphorylation states closely parallel changes of sleep need. SLEEPY, the mutant SIK3 protein, preferentially associates with and phosphorylates SNIPPs. Inhibition of SIK3 activity reduces phosphorylation of SNIPPs and slow wave activity during non-rapid-eye-movement sleep, the best known measurable index of sleep need, in both Sleepy mice and sleep-deprived wild-type mice. Our results suggest that phosphorylation of SNIPPs accumulates and dissipates in relation to sleep need, and therefore SNIPP phosphorylation is a molecular signature of sleep need. Whereas waking encodes memories by potentiating synapses, sleep consolidates memories and restores synaptic homeostasis by globally downscaling excitatory synapses.sup.4-6. Thus, the phosphorylation-dephosphorylation cycle of SNIPPs may represent a major regulatory mechanism that underlies both synaptic homeostasis and sleep-wake homeostasis.A subset of synaptic proteins are cumulatively phosphorylated during wakefulness and dephosphorylated during sleep, in accordance with sleep need; this may represent a common mechanism underlying regulation of both synaptic homeostasis and sleep-wake homeostasis.

High-throughput analyses of how sleeping fruit flies respond to a variety of odours show that the brains of these insects continue to process the value of the signals conveyed by sensory information during sleep. Food odours wake up hungry flies more than they wake up fed flies., Author(s): Wanhe Li, Alex C. Keene Author Affiliations: Flies sense the world while sleeping Sleep is a complex behaviour nearly ubiquitous among animal species[sup.1] [sup.,] [sup.2] . Many animals, including [...]

Author(s): Franz Weber [1]; Yang Dan (corresponding author) [1] Sleep is a seemingly unproductive behavioural state that takes up a large proportion of our lives, but insufficient sleep can profoundly [...], Sleep is a fundamental biological process observed widely in the animal kingdom, but the neural circuits generating sleep remain poorly understood. Understanding the brain mechanisms controlling sleep requires the identification of key neurons in the control circuits and mapping of their synaptic connections. Technical innovations over the past decade have greatly facilitated dissection of the sleep circuits. This has set the stage for understanding how a variety of environmental and physiological factors influence sleep. The ability to initiate and terminate sleep on command will also help us to elucidate its functions within and beyond the brain.