Large animal platform (LAP) for chronic testing of novel devices and biological responses
PIs
Prof. Volker Coenen
Dr. Máté Döbrössy
Summary
We have developed a large animal model (based on sheep) that can serve as an experimental platform in vivo in live and moving animals to test novel neuromodulatory strategies, stimulation and recording electrodes, or closed loop systems using brain-interface-components. The protocols permit us to carry out welfare and neurological monitoring, complex behavioral analysis, image-guided stereotactic brain surgery to implant ECoG electrodes and DBS electrodes reaching cortical or sub-cortical structures, as well as post-mortem tissue analysis to complement the investigations. The protocols and methodologies used satisfy the requirements for eventual clinical grade studies. The aim of the project is two-fold: Firstly, the LAP is used to improve our understanding of the sheep brain anatomy and connectivity with the main focus on the limbic, emotion and mode processing circuitries. Three main approaches are taken: i.) we have started acquiring pilot data using MRI based fiber tractography imaging from live, anaesthetized sheep to map out main projection pathways, including midbrain-forebrain connections; ii.) we have developed protocols to histologically process post-mortem sheep brain to identify, using antibodies or chemical stains, pathways or key biological markers/ molecules of interests e.g. neurotransmitter or immune response markers; and iii.) we are adapting our rodent protocols to the sheep to carry out monosynaptic anterograde and retrograde pathway tracing using viral tools in living animals. Secondly, LAP will serve as the experimental tool for in-vivo, chronic functional testing of biocompatibility and brain-interface-components, recording/ stimulating/ multi-function hybrid devices that have gone through initial rodent testing and that might be considered as candidates for medical/ therapeutic regulatory body approval. In summary, LAP contributes by strengthening the consortium's translational impact.