Research interests

We are interested to understand how the properties of individual synapses define information processing in neurons, networks of neurons and ultimately, behavior. We address this question by selective molecular perturbation of defined synapses combined with subsequent investigation of synaptic structure and function, as well as behavior. We achieve selective perturbation of pre- and postsynaptic proteins in the living organism by combining mouse genetics and viral technologies. The cellular level of analysis is carried out in brain slices using electrophysiology and imaging approaches. For example, a protein involved in synaptic vesicle docking is selectively deleted by viral expression of Cre recombinase in the brain of mice carrying conditional (floxed) alleles of this protein. This allows determination of structural and functional consequences in the context of a defined synaptic connection in vivo. After establishing the phenotype on the cellular level, the same expression approach is used to determine the effects of this perturbation on the behavior of the mice. We have established this integrated approach in the olfactory sytem, where we study the molecular and neuronal mechanisms of odor discrimination. Our main model system for presynaptic structure-function studies is the calyx of Held giant synapse, from which simultaneous pre- and postsynaptic recordings can be obtained. More recently, we have established new giant synapses in the thalamus as model systems for structure-function approaches. Finally, we also study the mechanisms of chloride regulation in neurons, which is fundamental to the function of GABAergic and glycinergic synapses. We use a genetically encoded indicator, Clomeleon, to determine neuronal chloride concentrations in vitro and in vivo.

 

Methods applied

Molecular biology, cell biology, production of recombinant proteins, viral gene transfer (AAV, LV, Sindbis, Adeno), high-precision stereotaxic delivery, brain slices, primary neuronal cell culture, electrophysiology, imaging genetically encoded probes, confocal imaging, multiphoton imaging, 3D image reconstruction and analysis, immunohistochemistry, electron microscopy, olfactory behavior.