The properly regulated secretion of neurotransmitters in the brain is essential for normal functioning of the brain. Many neurological and psychiatric diseases show a lack or an imbalance of neurotransmitters with severe consequences. Parkinson's disease, Alzheimer's disease, epilepsy, schizophrenia and depression are just a few examples of such diseases.
|Electron microscopy picture of a synapse from cultured hippocampal neurons.|
The study of the mechanism of synaptic neurotransmitter secretion is important for the understanding, diagnosis and the potential treatment of these diseases. The release of neurotransmitters in the brain occurs mainly via synaptic vesicle exocytosis. Synaptic vesicle proteins are thought to be important elements in this process. However the functional analysis of these proteins has been extremely difficult due to the lack of functional assays and in vitro systems. My lab studies the involvement of synaptic proteins in neuronal function by using genetic approaches. The generation of mice mutated in genes coding for synaptic proteins allows the analysis of protein function in a whole animal and can produce valuable models for neurological diseases. In previous studies we generated mutant mice using gene targeting by homologous recombination in embryonic stem cells. The effect of the inactivation of genes coding for different synaptic vesicle proteins was studied. The ablation of some of these genes leads to disturbance of the normal regulated synaptic transmission. This demonstrates that some synaptic vesicle proteins are involved in the regulation of the efficiency of synaptic connections.
We are using biochemical, physiological and genetic methods to study the molecular basic of this process. Furthermore we are generating new mice lines that are deficient in other synaptic proteins to understand their biological function. The analysis of these mice with different methods should help to clarify the role of the mutated proteins in synaptic transmission.
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