Neurophysiological models

As many aspects of synaptic function are still incompletely understood, there is a need to use accessible experimental models to study the precise mechanisms involved. Because of the complexity of the brain, research often relies on in vivo studies, mostly in mouse models. However, the Ehrlich team is promoting 3R research by replacing in vivo animal work, when possible, with studies in organotypic brain slice cultures of different mouse models, where slices of specific brain regions are maintained in a culture dish for several weeks. Slice cultures allow, for example, parallel drug testing or genetic manipulations on tissue from the same animal (ex vivo), and can replace animal experiments. In addition, ex vivo results facilitate the design of more directed experimental strategies in follow-up in vivo experiments, thus reducing the animal numbers.

Apart from easy accessibility for manipulations, a major advantage of organotypic slice cultures is that the network architecture, the different neuronal and non-neuronal cell types and their complex connections and interactions are well maintained, thus providing a close match to the in vivo situation. Limitations arise from the fact that the cultured brain region is disconnected from long-range in- and outputs, and neuromodulatory inputs, making it difficult to model processes underlying complex brain functions such as behavior.

The Ehrlich team uses organotypic cultures of the hippocampus, a brain region important for neurodevelopmental and neurodegenerative disorders affecting memory and cognition. Future goals include (1) expanding to culturing other brain regions relevant in other neurological disorders, and (2) in collaborative efforts develop more complex brain slice culture models that include the blood circulation (vascularization).