P2DS

The project aims to develop a novel predictive preclinical screening platform to reduce the prevailing high exclusion rate of drug discovery for psychiatric diseases. The development of new devices for drug testing will be linked to the establishment of a standardized in vivo model. Neuronal activity is measured by electrophysiological methods and activity patterns are compared in vitro and in vivo. Compared to conventional systems, additional specificity is achieved through the use of RNA interference methods both in vitro and in vivo. The approach is generally applicable for many questions. In this project, a feasibility study will be carried out using the example of post-traumatic stress disorders in which the GABA-A receptors play a specific role and represent sophisticated target structures for drug discovery.
In detail, microelectrode arrays are used for the derivation of signals from rats in vivo, whose behaviour in stress paradigms is measured in parallel with the derivation. The results are compared with those of conventional electrophysiological methods. In parallel, networks of cultured cortical neurons on microelectrode arrays will be derived in vitro in order to compare in vivo data with those from more powerful in vitro systems. By lentiviral transfer of RNA interference vectors, individual GABA-A receptors are down-regulated to investigate the involvement of specific receptor subunits for behavior and synaptic function and for the specificity of drugs both in vitro and in vivo. Finally, these vectors are also used to characterize changes in synaptic structures in experimental approaches.