Current biology : CB
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General anesthesia remains a mysterious phenomenon, even though a number of compelling target proteins and processes have been proposed [1]. General anesthetics such as isoflurane abolish behavioral responsiveness in all animals, and in the mammalian brain, these diverse compounds probably achieve this in part by targeting endogenous sleep mechanisms [2, 3]. However, most animals sleep [4], and they are therefore likely to have conserved sleep processes. ⋯ We studied general anesthesia in Drosophila by measuring stimulus-induced locomotion under isoflurane gas exposure. Using a syntaxin1A gain-of-function construct, we found that increasing synaptic activity in different Drosophila neurons could produce hypersensitivity or resistance to isoflurane. We uncover a common pathway in the fly brain controlling both sleep duration and isoflurane sensitivity, centered on monoaminergic modulation of sleep-promoting neurons of the fan-shaped body.
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Two clichés of science journalism have now played out around the ENCODE project. ENCODE's publicity first presented a misleading "all the textbooks are wrong" narrative about noncoding human DNA. Now several critiques of ENCODE's narrative have been published, and one was so vitriolic that it fueled "undignified academic squabble" stories that focused on tone more than substance. Neither story line does justice to our actual understanding of genomes, to ENCODE's results, or to the role of big science in biology.
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Current biology : CB · Feb 2013
ReviewSpatial sensory organization and body representation in pain perception.
Pain is a subjective experience that protects the body. This function implies a special relation between the brain mechanisms underlying pain perception and representation of the body. All sensory systems involve the body for the trivial reason that sensory receptors are located in the body. ⋯ We argue that pain perception involves some of the representational properties of exteroceptive senses, such as vision and touch. Pain, however, has the unique feature that the content of representation is the body itself, rather than any external object of perception. We end with some suggestions regarding how linking pain to body representation could shed light on clinical conditions, notably chronic pain.
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Current biology : CB · Nov 2012
Two dopaminergic neurons signal to the dorsal fan-shaped body to promote wakefulness in Drosophila.
The neuronal circuitry underlying sleep is poorly understood. Although dopamine (DA) is thought to play a key role in sleep/wake regulation, the identities of the individual DA neurons and their downstream targets required for this process are unknown. ⋯ These experiments define a novel arousal circuit at the single-cell level. Because the dorsal fan-shaped body promotes sleep, these data provide a key link between wake and sleep circuits. Furthermore, these findings suggest that inhibition of sleep centers via monoaminergic signaling is an evolutionarily conserved mechanism to promote arousal.
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Current biology : CB · Nov 2012
Direct activation of sleep-promoting VLPO neurons by volatile anesthetics contributes to anesthetic hypnosis.
Despite seventeen decades of continuous clinical use, the neuronal mechanisms through which volatile anesthetics act to produce unconsciousness remain obscure. One emerging possibility is that anesthetics exert their hypnotic effects by hijacking endogenous arousal circuits. A key sleep-promoting component of this circuitry is the ventrolateral preoptic nucleus (VLPO), a hypothalamic region containing both state-independent neurons and neurons that preferentially fire during natural sleep. ⋯ Cumulatively, this work demonstrates that anesthetics are capable of directly activating endogenous sleep-promoting networks and that such actions contribute to their hypnotic properties.