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Analysis of the sleep homeostat of the nematode Caenorhabditis elegans

dc.contributor.advisorBringmann, Henrik Dr.
dc.contributor.authorSpies, Jan-Philipp
dc.date.accessioned2015-12-21T09:24:23Z
dc.date.available2015-12-21T09:24:23Z
dc.date.issued2015-12-21
dc.identifier.urihttp://hdl.handle.net/11858/00-1735-0000-0028-867B-8
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-5437
dc.language.isoengde
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc570de
dc.titleAnalysis of the sleep homeostat of the nematode Caenorhabditis elegansde
dc.typedoctoralThesisde
dc.contributor.refereeStumpner, Andreas Prof. Dr.
dc.date.examination2015-02-20
dc.description.abstractengSleep is essential for animal life and conserved in all animals that have a nervous system. The nematode Caenorhabditis elegans exhibits sleep that is regulated homeostatically during larval development. However its regulation is poorly understood. The aim of this thesis was to gain a better understanding of the neuronal and molecular mechanisms underlying sleep homeostasis. To investigate the sleep homeostat of C. elegans, I developed an automated sleep deprivation setup based on mechanical stimulation/optogenetics allowing simultaneous behavioral analysis and functional imaging of neurons. I have identified RIS as the neuron reflecting the sleep homeostat and several molecules underlying sleep using genetic approaches and in vivo neuronal imaging. I found that sleep deprivation significantly shortens the animals sleeping duration and yields persistent increased locomotion past the deprivation period. To look for homeostatic changes in sleep intensity, I investigated the effect of sleep deprivation on the mechanosensory neuron ALM using calcium imaging. Prolonged sleep deprivation induces a significant decrease in stimulus-evoked ALM calcium transients compared to a wake control. In addition to this homeostatic regulation of ALM responsiveness I found that quiescence is already induced while the deprivation stimulus still yields strong activation of ALM. I show that this quiescence is induced by the interneuron RIS. Hence, RIS reflects the homeostat actively driving quiescence as a response to sleep deprivation. Moreover I demonstrate that RIS has a more general function on the homeostatic regulation of locomotion. Both spontaneous locomotion and evoked locomotion are dampened by RIS activation. The fact that RIS controls both the balance between mobility and immobility and the sleep homeostat suggests a related evolutionary origin. By reverse genetic approaches I found that the transcription factor lim-6 which is known to regulate RIS differentiation, is required for wild-type sleep. However, RIS activity at sleep onset and in response to sleep deprivation is similar to wild-type. I demonstrate that the neurotransmitters serotonin, dopamine, GABA, glutamate, and octopamine are not individually essential for the sleep homeostat. Furthermore I found that GABA, glutamate, and octopamine knockout mutants do not show altered RIS activity. egl-3 knockout mutants which have defects in the synthesis of neuropeptides, show RIS overactivation in the mid and late sleep phase while barely immobilizing during sleep. This implies that neuropeptide signaling is required downstream of RIS for the induction of quiescence. Finally, ion channel modulation is widely associated with sleep and sleep homeostasis. I demonstrate that the inositol trisphosphate receptor itr-1(sa73) KO mutant, has a reduced RIS sleep onset peak. I show that the calcium channel α2/δ subunit unc-36 knockout mutant exhibits long lasting RIS overactivation during sleep.de
dc.contributor.coRefereeFrahm, Jens Prof. Dr.
dc.subject.engSleepde
dc.subject.engCaenorhabditis elegansde
dc.subject.engIn vivo calcium imagingde
dc.subject.engSleep deprivationde
dc.identifier.urnurn:nbn:de:gbv:7-11858/00-1735-0000-0028-867B-8-1
dc.affiliation.instituteBiologische Fakultät für Biologie und Psychologiede
dc.subject.gokfullBiologie (PPN619462639)de
dc.identifier.ppn844760218


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