Neuronal signalling pathways: Stabilization of synapses
The malfunction of genes responsible for the formation and stabilization of synapses plays an important role in the development and progression of diseases of the central nervous system. Consequently, neurodegenerative and mental disorders are associated with a change in size and the loss of excitatory and inhibitory synapses in specific areas of the brain.
We are investigating the molecular mechanisms of synapse formation and stabilization in vitro and in vivo. To this end, gene transfer methods (viral RNA interference or overexpression of mutated proteins) are combined with immunohistochemical methods. 3D reconstruction of immunostained synapses is employed to quantify synapses in tissue or cell cultures.
In inhibitory synapses, GABAA receptors are organized by means of submembrane gephyrin clusters. We investigate transmembrane receptors and neuronal signalling pathways that control the number and size of gephyrin clusters. For example, we found the cell adhesion molecule neurofascin, which is expressed on the axon initial segment, to be involved in the stabilization of gephyrin clusters in vivo. This function is regulated through the interaction with FGFR1.
Current research topics:
- GABAA receptors in posttraumatic stress disorders (P2DS)
- Synaptic stability in neurodegenerative diseases (Mitomodels)
- Signal transduction of gephyrin clustering
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