EUCLOCK - Entrainment of the circadian clock - - Doctoral position open (Allocations de recherche)

(Sept 2007- Sept 2010)

The research will be conducted in the newly established CNRS European Associated Laboratory for Circadian Biology (Frankfurt/Strasbourg), the Max Planck Institute for Brain Research (Frankfurt) and the Institute for Cellular and Integrative Neurosciences (Strasbourg). For the project (timing in the brain: circadian regulation of the lateral hypothalamus) we have a doctoral position for 3 years starting September 1st 2007. The Ph’D will be prepared in “co-Direction” between Strasbourg and Frankfurt (H Meissl and P. Pevet).
Applications are invited from researchers in the natural sciences with a background in electrophysiological techniques, and a genuine interest in systems neuroscience. Knowledge of English and/or German is required.
Applications including CV, and the names of academic referees should be sent to:
Dr. Dr P. Pevet
Institut des Neurosciences Cellulaires et Int�gratives
UMR/LC2 7168 CNRS-Universit� L. pasteur
5 rue Blaise Pascal, 67084 Strasbourg
France
Tel (33)3 88 45 66 08
Fax (33)3 88 45 66 54
Mail: [email protected]

Title: Timing in the Brain: Circadian Regulation of the Lateral Hypothalamus

Daily and seasonal rhythmicity of physiological, endocrine and behavioral processes are temporal adaptations of all eukaryotic organisms to predictable changes in the environment. Rhythmic processes are driven by circadian clocks in the brain consisting of a central clock in the suprachiasmatic nucleus in the hypothalamus (SCN), other brain clocks like food-entrainable oscillators in the brain as well as peripheral oscillators in conjunction with associated input and output mechanisms, by which the clocks are synchronized (entrained) to local time and confer rhythmicity to other brain systems.
The present knowledge of the multi-oscillatory nature of the circadian system has modified the former view of a single master oscillator controlling peripheral slave oscillators towards a system consisting of different rhythmic components that are coupled by neuronal feedback pathways.

The aim of the PhD project is to investigate the influence of the SCN clock on its hypothalamic projection sites and the regulation of clock components by feedback mechanisms from these targets to the clock. Two identified targets of efferent projections of the SCN will be predominantly studied: 1) the arcuate nucleus, which is crucial for the maintenance of energy homeostasis; and 2) the lateral hypothalamus with the dorsomedial and ventromedial nuclei, regions implicated in the control of mammalian feeding behaviour. Both nuclei are additionally associated with the control of sleep-wakefulness, neuroendocrine homeostasis, and autonomic regulation. Recent neuroanatomical tracing studies provide evidence that the SCN receives direct inputs from both nuclei. These feedback signals could modulate the activity of the circadian clock. The present project concerns an investigation of the intimate relationship between these nuclei and the circadian clock in the SCN.

To address this issue, it is planned to use electrophysiological methods (conventional patch-clamp recordings and multi-microelectrode recordings from brain slices and/or dissociated primary cell cultures of the SCN and its target areas) and to assess the action of putative hormonal and neuronal signals (eg. orexins, ghrelin, and leptin) on the clock mechanism. On brain slices, targeted disruption of the neuronal pathways between the different nuclei using neurotoxins shall assist in the identification of response mechanisms. In dissociated primary SCN cell cultures, administration of hormones or neurotransmitters will allow validation of the data. Experiments will be carried out in rats or in different mouse models such as the orexin knock-out mice.
All equipment for patch-clamp recordings from brain slices or primary cell cultures as well as equipment for multi-microelectrode recordings is available.