Neurobiology and Genetics

    Closed Projects

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    Closed Research Projects

    The ability to synchronize to the cyclical changes in the environment is a fundamental property of circadian clocks. To do so, they use the light-dark cycles as most important Zeitgeber and temperature cycles as the second Zeitgeber. However it is largely unknown how the two informations are integrated by the clock. The clock of the fruit fly consists of different interacting clock neurons that give rise to two activity peaks per day - one in the morning and the other in the evening. Light accelerates the oscillations of one group of the clock neurons whereas it slows down that of the others, so that the morning activity is advanced and the evening activity delayed under long summer days. This response is mediated by rhodopsins in the compound eyes. In addition the compound eyes mediate direct light responses of the flies, such as an immediate activity increase when lights are shut on. In this project we want to clarify the roles of the 6 different rhodopsins in the eyes (Rh1, Rh3, Rh4, Rh5, Rh6 und Rh7) for the different responses. Furthermore, we investigate how temperature cycles and light-dark cycles are integrated by the clock neurons.

    The fruit fly Drosophila melanogaster – is successfully used as model system to understand the function of endogenous clocks. As in mammals, several clock neurons interact in a neuronal network with neuropeptides as main communication signals. The best investigated neuropeptide in Drosophila’s clock is the "pigment-dispersing-factor" (PDF). PDF is expressed in 4 small and 4 large neurons per brain hemisphere and serves as coupling signal between the different clock neurons as well as as output signal to downstream neurons. Besides the PDF-positive neurons, neurons that express the short or long form of Neuropeptid F (NPF) and neurons expressing the Ion Transport Peptide (ITP) are important for the function of endogenous clock. The aim of the project is to classify their role in the circadian system and to unravel their action on other neurons by in vivo Ca2+ and cAMP-Imaging (Details see project of Christiane Hermann).

    Chronic psychosocial stress and dys-regulation of the circadian clock share many common features. Both have dramatic consequences on health and life span, both prominently affect the HPA axis influencing glucocorticoid (GC) levels and immune responses, and both employ similar neuropeptides as signalling molecules. Anatomically, the HPA axis and the circadian clock in the suprachiasmatic nuclei (SCN) share a common interface - the paraventricular nucleus (PVN). Within the PVN, corticotrophin releasing factor (CRF) synthesizing neurons are stress responsive and trigger adrenal GC secretion. The PVN also receives inputs from the SCN, which regulates the circadian rhythm of GC secretion independent of stress. The daily GC peak prepares the animal for its active phase. This project will investigate the mutual interactions between psychosocial stress and the circadian clock in the SCN. We will determine (i) whether the circadian clock modulates the capability to cope with stress in a daytime dependent manner and (ii) whether psychosocial stress affects the circadian clock in dependence on the time of stressor exposure. To do so, we will subject mice to repeated social defeat (SD) stress in the morning or evening and investigate the physiological stress responses as well as the consequences on rhythmic behaviour and molecular circadian oscillations in the SCN.

    The homeostasis of transmitters is essential for normal brain function and glia cells play an essential role in it. Disturbances of this homeostasis result for example in an abnormal sleep-wake pattern. This project will investigate the regulation of monamine release (specially of dopamine and serotonin) by postulated tripartite synapses between monaminergic neurons, glia cells and circadian clock neurons of the fruit fly Dosophila melanogaster.

    In fruit flies, a mutation in the alanyltransferase "Ebony" that is exclusively expressed in glia cells results in disturbed sleep-wake patterns. Morphological investigations (confocal and EM) will show whether the postulated tripartite synapses exist. Sleep-wake studies of mutants with disturbed monamine transport and processing are planned to unravel the processes at synapses that lead to normal sleep. Ca++-imaging and period-luciferase imaging on cultivated brains will be performed to study the response of circadian clock neurons and glia cells to monamine transmitters as well as drugs that influence monaminergic signalling.