Poster Presentation No 1 Day 2- July 24 (12:40-14:10) Day 3- July 25 (12:40-14:10) TOWARDS AN INTEGRATIVE CONCEPT OF CIRCADIAN PROCESSES: A MATHEMATICAL MODEL OF SLEEP-WAKE CYCLES BASED ON NEURONAL ACTIVITY AND SYNAPTIC PLASTICITY. Postnova S, Braun HA Institute of Physiology, Philipps University, Marburg, German Background: Biological activity is undergoing circadian alterations which can be seen in many physiological parameters like blood pressure, cortisol secretion and body core temperature. The circadian alterations of all these functions are closely interlinked and all of them are somehow coupled to the most prominent and immediately evident circadian process, the sleep-wake cycle. Decoupling of the different rhythms is discussed as a source for chronic diseases, including disturbances of the cardiovascular system and hormone secretion or mood disorders. A better understanding of the interlinks between the different functions can be important for the prevention and treatment of such diseases. Methods: In search for the interlinks between circadian mechanisms our focus is laid on neuronal activity and synaptic transmission. All the circadian functions are under neuronal control of different synaptically connected nuclei of the. In a first step, we have developed a novel, neuron-based concept of sleep-wake cycles which we have realized in a mathematical model. Results: Our model connects the circadian pacemaker in the suprachiasmatic hypothalamic nuclei (SCN) to homeostatic mechanism which we assume to originate from alterations of the synaptic efficacy of hypocretin/orexin (hcrt/ox) neurons in the lateral hypothalamus (LH). These neurons are firing during wake and are silent during sleep. We propose that high frequent impulse activity of the hcrt/ox neurons during the wake state is sustained by reciprocal excitatory connections with local glutamate neurons. The transition to a silent state is going along with a weakening of the synaptic efficacy, which is recovering in the sleep (silent) state. With sufficiently strong input by the SCN or external stimuli (alarm clock) the circuit can be reactivated. This model can reflect major features of sleep-wake cycles. Summary: We present a novel mathematical model of sleep-wake cycles as a first step towards an integrative concept of circadian functions. It is based on neuronal activity and synaptic transmission and has the major advantage that it can be extended with physiologically plausible assumptions to consider related alterations of homeostatic functions, i.e. energy control, hormone release and thermoregulation, and to analyse their mutual interdependencies.
Poster Presentation No 2 Day 2- July 24 (12:40-14:10) Day 3- July 25 (12:40-14:10) COMPUTATIONAL AND SYSTEM-THEORETICAL EXAMINATION OF EXPERIMENTAL RECORDINGS FORM AFFERENT COLD FIBRES AND COLD NEURONS' SOMATA. Braun HA 1) , Huber MT 1,2) , Wollweber B 1,3) , Voigt K 1) 1) Institute of Physiology, Philipps University, Marburg, Germany 2) Psychiatry Hospitals, Stade, Germany 3) Max-Planck-Institute for Psychiatry, Munich, Germany. We have used a computational study of cold transduction to elucidate possible reasons for seemingly inconsistent experimental data which were obtained 1) with extracellular action potential recordings from afferent cold fibres (e.g. Braun et al., P flügers Arch . 386:1–9, 1980) and 2) with intracellular recordings of membrane potentials and ion currents from cold neurons' somata in the trigeminal and dorsal root ganglia (DRG). The latter attracted particular attention in suggesting cold and menthol sensitive TRP ion channels as the physiological correlate of cold sensation (e.g. McKemy et al., Nature 416:52-58, 2002; Peier et al., Cell. 108:705-715, 2002). The data from the cold neurons somata, however, are significantly different from those of peripheral receptors. Among others, they generally do show spontaneous discharges which is a major characteristic of cold receptors (Hensel et al. J. Physiol . 204: 99-112, 1969). Moreover, much stronger temperature changes are needed for the somata then for real receptors to induce transient responses and these occur only in a restricted temperature range. We assumed that the discrepancies might be due to the much bigger size of the somata compared to the receptors which means 1) higher membrane capacitance and 2) lower density of the functionally relevant ion channels in relation to the leak conductance. As this assumption cannot be proven experimentally we have used a previously developed computer model of cold receptors (Braun et al., Nova Acta Leopoldina . 88: 293-318, 2003) and could demonstrate that this model, indeed, can be converted into a soma model with increased capacitance and leak conductance: the spontaneous discharge was eliminated while the transient response persisted. We even could bring the model of the cell body back to spontaneous discharge with reduction of the K + -currents according to experimentally observed effects of 4-aminopyridine (de la Pena et al., J Physiol. 567: 415-426, 2005). However, although the response characteristics seem to be the same as those of the original model, a more thorough comparison over the full temperature range exhibit significant differences, especially with regard to the impulse pattern. From a system-theoretical point of view, the models operates at different dynamic states.
Poster Presentation No 3 Day 2- July 24 (12:40-14:10) Day 3- July 25 (12:40-14:10) PARALLEL PREOPTIC PATHWAYS FOR INHIBITION OF THERMOGENESIS Yoshida K 1) , Li X 2) , Ayoub I 1) , Cano G 3) , Lazarus M 4) , Saper CB 1) 1) Department of Neurology and Program in Neuroscience,Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA 2) Department of Cell Biology, College of Life Sciences at Wuhan University, Wuhan, Hubei, China 3) Department of Neurology, University of Pittsburg, Pittsburg, PA, USA 4) Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita, Osaka, Japan Sympathetic premotor neurons in the medullary raphe pallidus nucleus (RPa) appear to be a critical relay in the thermogenic pathway that increases body temperature under many physiological conditions. However, the origins of inputs to the RPa that activate it during cold exposure have not been definitively identified. We first investigated the origins of inputs to the RPa that show activation of cFos expression during cold exposure and showed that cold activated neurons projects to RPa are located only in the dorsomedial nucleus and dorsal hypothalamic area (DMH/DHA). We also showed that there are two separate preoptic cell groups, the median preoptic nucle (MnPO) and the dorsolateral preoptic area (DLPO), each of which send independent projections both to the RPa and to the DMH/DHA. We then showed that cell specific lesions of both the median or dorsolateral preoptic area release a thermogenic response with a 1.5 degree C elevation of body temperature and blockade of fever responses, whereas individual lesions of either cell group do not increase body temperature, and only lesions of the median preoptic nucleus prevent fever responses. These data identified two parallel descending preoptic pathways for regulating body temperature.
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