ominous raptorial shadow approaching from the front or the side…) This can be tested by asking mice - which swim quite well - to use visual cues of specific orientation to find a hidden platform in a bath of milky water. And indeed, Alzheimer mice need much bigger differences of orientation to know where a platform is hidden 80
2 | Cover of the Journal of Neuroscience, November 2012, Misgeld lab. Shown is a micrograph of the tail of a zebrafish larva, with nerve processes shown as black lines and neuronal mitochondria as blue dots.
than their non-diseased peers. Hence, the Konnerth lab could show that a cellular readout of circuit function can be directly correlated with a systemic behavioral deficit analogues of which are well known from human dementia patients.
sheath. Taking advantage of this, the Misgeld lab has succeeded in marking mitochondria in zebrafish and imaging them as sensory neurons grew and differentiated (Plucińska et al., J. Neurosci. 2012). In collaboration with the group of Prof. Christian Haass and Dr. Bettina Schmid at LMU Munich, Prof. Thomas Misgeld and colleagues used this new model to study how mitochondrial dynamism is disrupted when nerve cells are confronted with an Alzheimer-related protein - tau - that binds to the cytoskeleton. By modulating biochemical pathways that alter the strength with which tau binds the cytoskeleton, the Misgeld and collaborators could show that such transport deficits can be corrected. In addition to these scientific high-lights, the Neuroscience Focus Group had further progress to report in 2012: Both Prof. Arthur Konnerth and Prof. Misgeld became principle investigators in a new Cluster of Excellence, the “Munich Cluster for Systems Neurology” (SyNergy), which was established as part of the second round of the German “Excellence Initiative”. With Prof. Misgeld as co-coordinator, this Cluster's concept is heavily influenced by the “systems neuroscience” approach of the TUM-IAS Neuroscience Focus Group. In addition to this, the “Center of Integrated Protein Science Munich” (CIPSM) also received renewal funding - with Prof. Konnerth as coordinator of one Focus Group and Prof. Misgeld as associated PI. Prof. Konnerth was awarded a European Research Council (ERC) Advanced Grant, one of the most prestigious research awards in Europe. Prof. Misgeld received tenure at TUM in 2012, which successfully completed the “tenure track” process that was initiated by TUM-IAS in 2007. Further, he was appointed as associate member of the German Center of Neurodegenerative Diseases Munich and was awarded the Alzheimer Research Award of the Hans und Ilse Breuer Foundation. Selected Publications
While the Konnerth lab's work focused on how to integrate single-cell activity in the systemic context of circuits and behavior, the Misgeld group studied how the dynamism of a certain organelle - energy-producing mitochondria - plays out in the entirety of processes that a neuron forms. While mitochondrial dynamics are widely studied in cells isolated from the organism, few studies have so far succeeded to follow such dynamism in neurons that exists in their natural context. Indeed, this is not easy to do, as neurons form very extensive processes, and few animals allow imaging such cells in their entirety.
[1] C. Grienberger and A. Konnerth, “Imaging calcium in neurons,” Neuron, vol. 73, no. 5, pp. 862 – 85, 2012. [2] C. Grienberger, N. L. Rochefort, H. Adelsberger, H. A. Henning, D. N. Hill, J. Reichwald, M. Staufenbiel, and A. Konnerth, “Staged decline of neuronal function in vivo in an animal model of Alzheimer's disease,” Nature Comm., vol. 3, 774, 2012. [3] G. Plucińska, D. Paquet, A. Hruscha, L. Godinho, C. Haass, B. Schmid, and T. Misgeld, “In vivo imaging of disease-related mitochondrial dynamics in a vertebrate model system,” J. Neurosci., vol. 32, no. 46, pp. 16203 –16212, 2012. [4] P. Marinković, M.S. Reuter, M.S. Brill, L. Godinho, M. Kerschensteiner and T. Misgeld, “Axonal transport deficits
The zebrafish is an exception, as its larval stages are almost transparent, and the sensory neurons innervating its skin are arranged in a nearly two-dimensional
and degeneration can evolve independently in mouse models of amyotrophic lateral sclerosis,” Proc. Natl. Acad. Sci. USA, vol. 109, no. 11, pp. 4296 – 4301, 2012.