Director of the ZNZ
Institute of Pharmacology and Toxicology
University of Zurich
Room 17 J 64
Tel. +41 44 635 5926
Fax +41 44 635 6874
Keywords: synapse formation and plasticity; inhibitory neurotransmission; GABAA receptors; mutant mice; adult neurogenesis; epilepsy; seizures; inflammation; neurodegeneration
2 postdocs, 6 PhD students, 2 Master students, 2 technicians, 1 secretary
A major topic of research is the functional organization and plasticity of the GABAergic system, using a multidisciplinary approach ranging from molecular and cell biology to immunoelectron microscopy. In vitro experiments in primary neuronal cultures transfected with plasmids of interest provide a powerful tool to study the molecular mechanisms of synapse formation and plasticity. Our main working hypothesis is that the postsynaptic scaffold formed by gephyrin is a hub integrating multiple signaling cascades to regulate GABAA receptor function and to mediate cross-talk with excitatory synapses. In addition, transgenic mice expressing reported genes in neurons of interest, as well as mutant mice with targeted gene deletions affecting the GABAergic system, are essential to our in vivo experiments and our morphological studies using light and electron microscopy.
In this context, adult neurogenesis represents a powerful model to investigate the role of GABAergic transmission in the regulation of neuronal proliferation, differentiation, and synaptic integration. Perturbing GABAergic signaling by targeted mutagenesis or over-expression/silencing of mutant synaptic proteins selectively in adult born neurons allows investigating their effects in a physiologically normal environment. This work is conducted in mice lacking specific GABAA receptor subtypes and uses retro- and lentiviruses for transfecting newborn cells, followed by morphological and functional analysis.
Animal models are essential tools for investigating cellular and molecular alterations contributing to neurological and psychiatric disorders. To this end, we are working with mouse models of temporal lobe epilepsy and neurodegenerative diseases (Alzheimer, Parkinson), with a specific focus on neuro-immune interactions and the contribution of inflammation to pathophysiology of these brain diseases. Further, we investigate potential interactions between synaptic dysfunction in Alzheimer’s disease and epilepsy in these animal models.
Immunohistochemistry: single and multiple labeling studies in tissue sections and cell cultures; immunoelectron microscopy; in situ hybridization histochemistry
Molecular Biology; protein biochemistry; cell line (COS, HEK, Hela) cultures, rat primary neuron cultures, transfection by magnetofection
Stereotaxic surgery, intracerebral virus injections, EEG recordings
Microscopy and imaging: Confocal laser scanning microscopy and epifluorescence microscopy; live-imaging of cultured neurons; computer-based image analysis and densitometry
Main equipment: Zeiss LSM 710 Zen and LSM 700 Zen confocal laser scanning microscopes; Zeiss Apotome; Leica inverse microscope for live-cell microscopy; image analysis systems (MCID, Mercator, ImageJ, Imaris); standard equipment for molecular biology, biochemistry, histology and autoradiography, cryostat, microtome, cell culture facilities.
All major protocols used in our laboratory can be downloaded from our website (see link below)
Swiss National Science Foundation
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