Grant: Team Grant: Mental Disorders

Schizophrenia is characterized by profound disruptions in cognition and emotion. Despite pharmaco-therapeutic progresses, a considerable percentage of patients has no or only partial response to treatment. Development of more efficacious treatments is indispensible but crucially depends on an advanced elucidation of the progressive pathophysiological mechanisms underlying schizophrenia. Given methodological and ethical limitations of human studies, the use of appropriate and valid animal models of schizophrenia is a promising tool for such endeavours. The present project uses the maternal immune stimulation rat model of schizophrenia and deep brain stimulation (DBS) as an investigative tool to modulate neural activity of selected brain areas and associated networks in order to i) correlate the emergance of a schizophrenic phenotype with the development of dysfunctions at different levels of neurobiological integrity; ii) study bi-directional consequences of DBS and iii) study the preventive potential of pre-symptomatic activity-modulation on the emergence of behavioral and neurobiological abnormalities. The project will foster our understanding of dysfunctional neural circuitries in schizoprenia and set a strong interdisciplinary foundation for the translational application and advancement of DBS as a novel focal and causative strategy in the treatment of therapy-resistant schizophrenia.