Zentrum Physiologie und Pathophysiologie
Fon: +49-551-39 9677
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Calcium signals represent a key information processing system in the central nervous system, and defined changes in cytosolic calcium levels have been associated with multiple neuronal processes including learning, memory, synaptic plasticity, but also hypoxia and neurodegenerative disease. While the last years have provided a large amount of information about the molecular elements that control calcium signals in identified cells, little is known about how Ca-dependent signal cascades are processed, superimposed and integrated in a functionally intact neuronal net. Based on functionally intact motoneurons in the brain stem slice preparation from mice, we have addressed three questions:
i ) which molecular elements control Ca-dependent signal cascades associated during rhythmic activity in identified brain stem motoneurones ?
ii) how does the spatio-temporal profile of cytosolic Ca signaling modulate neuronal activity in this interconnected neuronal net ?
iii) how are cytosolic Ca signals affected in transgenic mouse models of human neurodegenerative disease (e.g. SOD1 G93A mouse model of human amyotrophic lateral sclerosis) that specifically affect motoneurones in the brain stem and spinal cord?
We address these questions by a combined research approach. For example, we employ techniques from molecular biology and classical electrophysiology like single cell PCR and patch clamp recordings from slice preparations and combine these measurements with up-to date imaging techniques like fast CCD imaging and IR-laser based multiphoton measurements. By utilizing these experimental tools, our research focus is to understand Ca signaling in functionally intact motoneurons, and achieve a better understanding of the disruptions of Ca-dependent signal cascades associated with ALS-related neurodegenerative disease.
Lips, M.B. and Keller, B.U. (1998). Endogenous calcium buffering in motoneurones of the
nucleus hypoglossus from mouse. J. Physiol., 511(1), 105-117.
Palecek, J., Lips, M. B. and Keller, B.U. (1999). Calcium dynamics and buffering in motoneurones of the mouse spinal cord. J. Physiol., 520 (2), 485-502.
Lips, M. and Keller, B.U. (1999). Activity-related calcium dynamics in motoneurones of the nucleus hypoglossus from mouse. J. Neurophysiol. 82 (6), 2936-2946 .
Paarmann, I., Frermann, D., Keller, B.U. and Hollmann, M. (2000). Expression of fifteen glutamate receptor subunits and various splice variants in tissue slices and single neurones of brainstem nuclei, and potential functional implications. Journal of Neurochemistry, 74 (4): 1335-45.
Ladewig T. and Keller, B.U. (2000). Simultaneous patch clamp recording and calcium imaging in a rhythmically active neuronal network in the brain stem slice preparation from mouse. Pflügers Arch., 440: 322-332.
Vanselow, B. and Keller, B.U. (2000). Calcium dynamics and buffering in oculomotor neurones from mouse. that are particularly resistant during amyotrophic lateral sclerosis (ALS)-related motoneuron disease. J. Physiol., 525: 433-445.
Ladewig T., Kloppenburg, P., Lalley, P.M., Zipfel, W.R., Webb, W.W. and Keller, B.U. (2003). Spatial profiles of store-dependent calcium release in motoneurones of the nucleus hypoglossus from newborn mouse. J. Physiol., 547: 775 - 787.
Bergmann, F. and Keller, B.U. (2004). Impact of mitochondrial inhibition on excitability and cytosolic Ca levels in brain stem motoneurons. J. Physiol., 555: 45 - 59