Linking synaptic dysfunction to disease mechanisms in schizophrenia - a multi-level investigation
Schizophrenia (SZ) is a serious mental illness characterized by frequent episodes of hallucination, delusions, and cognitive disabilities. SZ represents one of the major challenges for society, with large unmet patient needs and substantial health care costs. Synaptic dysfunction has recently been implicated in the pathophysiology of SZ, yet the precise mechanisms remain elusive. The SYNSCHIZ project targets synaptic dysfunction at multiple levels of investigation, from its genetic underpinnings through experimental investigation of electrophysiological properties in stem cell derived neurons and advanced mathematical modeling up to the level of brain network dysfunction in individuals with SZ. Thus, SYNSCHIZ aims to uncover how SZ risk genes yield aberrant neuronal excitability and brain connectivity to determine novel pathways and mechanisms. Furthermore, the project has a strong translational focus to transfer scientific discoveries into clinical applications, aiming at identification of clinically useful biomarkers. To reach these ambitious aims, our transdisciplinary network of scientific experts will provide synergy by performing a series of integrated collaborative studies. Thus, we will gain novel knowledge and ensure it will be applied in clinical settings. Our multi-level investigations will substantially improve our understanding of the pathophysiology of SZ and stimulate new developments for treatment and potential prevention of mental illness.
Gene targeting in the brain, Epilepsy, Computational neurosciences, Stem cells and neural differentiation/cell therapy, Molecular modelling techniques, schizophrenia, Imaging techniques, Pharmacology, Electrophisiological approaches, Behavioural methodologies, fMRI, (epi)genetic approaches, methylation, Intellectual disability, omics approaches, animal model, dentate gyrus, Stem cells and, neural differentiation/cell therapy, risk genes, synapse function and excitability, EEG, Bayesian tools, iPSC derived neurons, computational modeling, omics approaches, SNAREopathy, synaptic dysfunction, in vivo drug screen, in vitro drug screen, NMR, Translational, Multidisciplinary, Synaptopathy, iPSC, Organoid, human brain models, SYNGAP1, rats, post-traumatic stress disorder, brain circuits, functional magnetic resonance imaging, diffusion tensor imaging, inducible gene expression system, silencing of synaptic output, memory engram, basolateral amygdala, medial prefrontal cortex, locus coeruleus
2018 - 2021
Ole Andreassen (Coordinator)
The Netherlands (NWO)