Towards human synaptic physiology for psychiatric research

Abstract

We have performed a multi-scale synaptic analysis of mouse models of psychiatric disorders and found some candidate phenomena for the pathophysiology of the disorders. However, mouse models alone will not be sufficient to elucidate human psychiatric disorders. I believe that the combinatorial use of human-derived neurons, theoretical neuroscience and reverse translational feedback to mouse research is key. Human-derived samples include post-mortem brains, human iPSC-derived neurons and neurosurgically removed acute brain samples. While such human data can provide invaluable insights, they do not by themselves lead to an understanding of human disease. Therefore, to bridge the gap between the obtained "human data" and "our questions", we also use computational methods and integrate the human data into mathematical models, specifically the NEURON model, the Leaky Integrate-and-Fire model and the Free Energy model, and construct neuronal, circuit and behavioural models that implement the human parameters. In the talk I will present our current challenge of a rapid circulation between mouse, human and theoretical neuroscience to understand human psychiatric disorders.