title: Identification of Neurons with a Privileged Role in Sleep Homeostasis in Drosophila melanogaster.
abstract: Sleep is thought to be controlled by two main processes: a circadian clock that primarily regulates sleep timing and a homeostatic mechanism that detects and responds to sleep need. Whereas abundant experimental evidence suggests that sleep need increases with time spent awake, the contributions of different brain arousal systems have not been assessed independently of each other to determine whether certain neural circuits, rather than waking per se, selectively contribute to sleep homeostasis. Using the fruit fly, Drosophila melanogaster, we found that sustained thermogenetic activation of three independent neurotransmitter systems promoted nighttime wakefulness. However, only sleep deprivation resulting from activation of cholinergic neurons was sufficient to elicit subsequent homeostatic recovery sleep, as assessed by multiple behavioral criteria. In contrast, sleep deprivation resulting from activation of octopaminergic neurons suppressed homeostatic recovery sleep, indicating that wakefulness can be dissociated from accrual of sleep need. Neurons that promote sleep homeostasis were found to innervate the central brain and motor control regions of the thoracic ganglion. Blocking activity of these neurons suppressed recovery sleep but did not alter baseline sleep, further differentiating between neural control of sleep homeostasis and daily fluctuations in the sleep/wake cycle. Importantly, selective activation of wake-promoting neurons without engaging the sleep homeostat impaired subsequent short-term memory, thus providing evidence that neural circuits that regulate sleep homeostasis are important for behavioral plasticity. Together, our data suggest a neural circuit model involving distinct populations of wake-promoting neurons, some of which are involved in homeostatic control of sleep and cognition.
authors.affiliation: Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Glen
authors.initials: G
authors.lastname: Seidner
authors.affiliation: Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Robinson
authors.affiliation: Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, CA 94720, USA.
authors.forename: Kurtresha
authors.initials: K
authors.lastname: Worden
authors.affiliation: Department of Biological Sciences, Binghamton University, Binghamton, NY 13902, USA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Masek
authors.affiliation: Department of Mechanical and Aerospace Engineering, University of California San Diego, La Jolla, CA 92093, USA.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Roberts
authors.affiliation: Department of Biological Sciences, Florida Atlantic University, Jupiter, FL 33458, USA.
authors.forename: Alex C
authors.initials: AC
authors.lastname: Keene
authors.affiliation: Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA; Neurosciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA; Center for Circadian Biology, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: wjoiner@ucsd.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Joiner
mesh_terms: D000818:Animals; D001143:Arousal / Q000502:physiology; D001921:Brain / Q000502:physiology; D002940:Circadian Rhythm; D004331:Drosophila melanogaster / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D023421:Models, Animal; D009474:Neurons / Q000502:physiology; D017982:Receptors, Biogenic Amine / Q000502:physiology; D012890:Sleep / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology
chemical_list: D017982:Receptors, Biogenic Amine; C027604:norsynephrine receptor