Neuroimmunology and Imaging
Dr. Martin Fuhrmann
Group Leader
Sigmund-Freud-Str. 27
53127 Bonn

martin.fuhrmann@dzne.de
 +49 228 43302-480

Areas of investigation/research focus

Alzheimer’s disease is characterized by two hallmarks, extracellular Ab-deposition and intracellular aggregation of hyperphosphorylated tau. Furthermore, synapse and neuron loss correlates well with cognitive decline. Sterile inflammation carried out by microglia that are part of the innate immune system in the brain, are in the focus of current research. We try to understand how these components contribute to learning and memory deficits under AD-like conditions. On the one hand, we investigate the hypothesis that an imbalance of excitation and inhibition related to synapse and neuron dysfunction contributes to neuronal network disturbance. In this direction we investigate how structural and functional deficits of GABAergic neurons in the hippocampus contribute to learning and memory deficits. On the other hand, we investigate how microglia contribute to synaptic and neuronal deficits. Especially, we are interested in the interaction of microglia with individual synapses and neurons and how that impacts on the integrity neuronal network connectivity. To address these questions we use state of the art in vivo imaging techniques and combine them with electrophysiological, histological and biochemical techniques in transgenic mice. Moreover, we use optogenetics and chemogenetics to specifically activate or inactivated neuronal subsets.

Key Publications

Schmid LC, Mittag M, Poll S, Steffen J, Wagner J, Geis HR, Schwarz I, Schmidt B, Schwarz MK, Remy S, Fuhrmann M. Dysfunction of Somatostatin-Positive Interneurons Associated with Memory Deficits in an Alzheimer's Disease Model. Neuron. 2016 Oct 05; 92:114-125. doi: 10.1016/j.neuron.2016.08.034
Jens Wagner, Sybille Krauss, Song Shi, Sergey Ryazanov, Julia Steffen, Carolin Miklitz, Andrei Leonov, Alexander Kleinknecht, Bettina Göricke, Jochen H. Weishaupt, Daniel Weckbecker, Anne M. Reiner, Wolfgang Zinth, Johannes Levin, Dan Ehninger, Stefan Remy, Hans A. Kretzschmar, Christian Griesinger, Armin Giese, Martin Fuhrmann. Reducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies. Acta Neuropathologica. 2015 Oct 31; 130:619-631. doi: 10.1007/s00401-015-1483-3
Ligang Gu, Stefanie Kleiber, Lena Schmid, Felix Nebeling, Miriam Chamoun, Julia Steffen, Jens Wagner, Martin Fuhrmann. Long-term in vivo imaging of dendritic spines in the hippocampus reveals structural plasticity. Journal of Neuroscience. 2013 Dec 31; 34:13948-13953. doi: 10.1523/JNEUROSCI.1464-14.2014
Fuhrmann M, Bittner T, Jung CK, Burgold S, Page RM, Mitteregger G, Haass C, LaFerla FM, Kretzschmar H, Herms J. Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer's disease. Nat Neurosci. 2010 Apr 01; 13:411-3. doi: 10.1038/nn.2511
Fuhrmann M, Mitteregger G, Kretzschmar H, Herms J. Dendritic pathology in prion disease starts at the synaptic spine. J Neurosci. 2007 Jun 06; 27:6224-33.

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