Understanding psychosis, cognitive impairment and motor symptoms induced by NMDA receptor dysfunction: from mechanisms to prevention and therapy
Here we propose a collaborative project in which we aim to identify in mouse models specific molecular and cellular determinants of psychosis, cognitive deficits and motor symptoms triggered by NMDAR dysfunction and to evaluate in a translational approach the effectiveness of D-serine in preventing/treating these abnormalities in schizophrenia. We aim to unravel in specific mouse models of NMDAR dysfunction molecular, cellular and circuit deficits associated with psychosis. The focus of the analysis of mouse models will be on following aspects: 1.The effect of cell-specific mechanisms on oscillatory activity and cognitive impairment associated with NMDAR-mediated psychosis; 2. The role of molecular determinants (subunit composition) in NMDAR-mediated psychosis; 3. Mechanisms of the complex locomotor effects of NMDAR blockade; 4. The effect of long-term NMDAR blockade on hippocampal atrophy/neuronal cell death; 5. The evaluation of the possible ?rescue? effect of treatment with D-serine; The clinical investigations will focus on two groups of patients with: a) prodromal and b) chronic therapy-resistant forms of schizophrenia. It will comprise neuroimagistic, psychometric, neurophysiological measures, as well as the examination of the role of genetic factors and the estimation of oscillatory patterns be complemented by reconstruction of functional connectivity patterns in patients and mouse models.
Imaging techniques, Gene targeting in the brain, Computational neurosciences, Molecular modelling techniques, schizophrenia, Imaging techniques, Electrophisiological approaches, Behavioural methodologies, fMRI, (epi)genetic approaches, chronic stroke, awake imaging, in vivo STED imaging, light sheet microscopy, MRI, multidimensional behavior analysis, Stem cells and, neural differentiation/cell therapy, risk genes, synapse function and excitability, EEG, Bayesian tools, iPSC derived neurons, computational modeling
2018 - 2021
Dragos Inta (Coordinator)