Rogdi Defines GABAergic Control of a Wake-promoting Dopaminergic Pathway to Sustain Sleep in Drosophila

Kohlschutter-Tonz syndrome (KTS) is a rare genetic disorder with neurological dysfunctions including seizure and intellectual impairment. Mutations at the Rogdi locus have been linked to development of KTS, yet the underlying mechanisms remain elusive. Here we demonstrate that a Drosophila homolog of Rogdi acts as a novel sleep-promoting factor by supporting a specific subset of gamma-aminobutyric acid (GABA) transmission. Rogdi mutant flies displayed insomnia-like behaviors accompanied by sleep fragmentation and delay in sleep initiation. The sleep suppression phenotypes were rescued by sustaining GABAergic transmission primarily via metabotropic GABA receptors or by blocking wake-promoting dopaminergic pathways. Transgenic rescue further mapped GABAergic neurons as a cell-autonomous locus important for Rogdi-dependent sleep, implying metabotropic GABA transmission upstream of the dopaminergic inhibition of sleep. Consistently, an agonist specific to metabotropic but not ionotropic GABA receptors titrated the wake-promoting effects of dopaminergic neuron excitation. Taken together, these data provide the first genetic evidence that implicates Rogdi in sleep regulation via GABAergic control of dopaminergic signaling. Given the strong relevance of GABA to epilepsy, we propose that similar mechanisms might underlie the neural pathogenesis of Rogdi-associated KTS

Insights into Sleep Homeostasis from a Drosophila Genetic Screen for Sleep Rebound Mutants

Sleep rebound—the increase in sleep that follows sleep deprivation (SD)—is a hallmark of homeostatic sleep regulation that is conserved across the animal kingdom. However, both the mechanisms that underlie sleep rebound and its relationship to other forms of homeostatic sleep regulation remain unclear. To identify mechanisms important for sleep rebound, we developed a novel method of inducing SD in Drosophila by thermogenetically activating wake-promoting neurons. We then used this method to conduct a large-scale genetic screen to identify Drosophila mutants with reduced sleep rebound. In Chapter 1, we discuss the use of Drosophila melanogaster as a model organism in sleep research. In Chapter 2, we discuss results of the genetic screen, where we find that sleep rebound and habitual sleep amount are controlled by separate genetic factors. In Chapter 3, we present data suggesting that mutants with reduced sleep rebound experience a milder wake-promoting stimulus during the sleep deprivation period compared to control flies, and that this difference in the strength of the wake-promoting stimulus is likely responsible for the reduced rebound phenotype. In Chapter 4, we discuss the implications of these data, and future directions to explore a model where homeostatic plasticity in the neural circuit used to produce sleep loss is responsible for subsequent rebound. These findings have important implications for our understanding of sleep and provide a model for homeostatic sleep regulation that could apply to mammalian systems

Insights into Sleep Homeostasis from a Drosophila Genetic Screen for Sleep Rebound Mutants

Sleep rebound—the increase in sleep that follows sleep deprivation (SD)—is a hallmark of homeostatic sleep regulation that is conserved across the animal kingdom. However, both the mechanisms that underlie sleep rebound and its relationship to other forms of homeostatic sleep regulation remain unclear. To identify mechanisms important for sleep rebound, we developed a novel method of inducing SD in Drosophila by thermogenetically activating wake-promoting neurons. We then used this method to conduct a large-scale genetic screen to identify Drosophila mutants with reduced sleep rebound. In Chapter 1, we discuss the use of Drosophila melanogaster as a model organism in sleep research. In Chapter 2, we discuss results of the genetic screen, where we find that sleep rebound and habitual sleep amount are controlled by separate genetic factors. In Chapter 3, we present data suggesting that mutants with reduced sleep rebound experience a milder wake-promoting stimulus during the sleep deprivation period compared to control flies, and that this difference in the strength of the wake-promoting stimulus is likely responsible for the reduced rebound phenotype. In Chapter 4, we discuss the implications of these data, and future directions to explore a model where homeostatic plasticity in the neural circuit used to produce sleep loss is responsible for subsequent rebound. These findings have important implications for our understanding of sleep and provide a model for homeostatic sleep regulation that could apply to mammalian systems

Sleep: A Neuropeptidergic Wake-up Call for Flies

Endogenous circadian rhythms exert strong effects on sleep, but the neuronal mechanisms that produce these effects have remained obscure. New work implicates neuropeptidergic signaling in a subset of circadian clock cells in the regulation of sleep late at night

Vergleichende Untersuchungen ueber Vorkommen und Bedeutung von Parasitosen bei Klinikpatienten in den Zeitraeumen 1969-1973 und 1979-1983

SIGLEAvailable from: Zentralstelle fuer Agrardokumentation und -information (ZADI), Villichgasse 17, D-53177 Bonn / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Opto-mechanical alignment results of the Euclid near infrared spectro-photometer optical assembly NI-OA

The Euclid payload features two instruments that are observing the sky simultaneously. The visual light high spatial resolution imager (VIS) and the Near Infrared Spectrometer and Photometer (NISP). A Korsch type telescope with 1,2m diameter feeds both instruments via a dichroic beamsplitter. The NISP instrument reduces the incoming f/#20 beam of the telescope to an f/# 10 beam. The instruments optical system, the NISP Optical Assembly (NI-OA) contains 4 lenses, one single lens in front of a Grism and Filter wheel which is called collimator lens assembly (CoLA), and a lens triplet between these Grism and Filter wheel and the instruments focal plane, which is called camera lens assembly (CaLA). The focal plane consists of 16 Hawaii 2RG detectors. The required alignment accuracy of the lens triplet and of the singlet relative to the triplet is very demanding and needs to be achieved and verified at the operational temperature of 134K. As an introduction the design, the integration and alignment concept are briefly summarized, as well as the measurement concept to verify the cold alignment within the cryostat. Alignment results for the integration of CaLA EQM and FM at room temperature are presented, the alignment stability after vibrational loads and thermal vacuum cycling is high, only minor changes of a few μm and arcsecs can be detected. The accuracy of the measured cryogenic alignment is demonstrated to be just a few μm and arcsec off the ideal predicted opto-mechanical alignment