MPI-NAT Symposium: Hallucinating mice, neural circuits and immunity – towards mechanistic treatments for psychosis

Psychosis, defined by disturbances of perception and thought, is a core feature of severe mental illness, yet no mechanistic treatments are currently available. A major barrier to progress is the difficulty of modelling psychosis in animals. In our research, we develop and exploit cross-species frameworks for the mechanistic study of psychosis. To measure psychosis phenotypes in mice, we devised a novel behavioural-computational paradigm to quantify hallucination-like perception across species. This approach revealed that striatal dopamine and acetylcholine critically shape perceptual inference, identifying candidate neuromodulatory targets for treatment. To induce psychosis-like states in mice, we established a new model of autoimmune psychosis. We showed that brain-reactive autoantibodies can trigger microglial phagocytosis and psychosis-like behaviour, and that antipsychotic drugs may act through immunomodulatory effects, opening the door for immunological treatments. Ongoing work investigates how neural and immune signals interact to drive psychosis. In mice, we dissect mechanistic pathways. In patients, we define behavioural and immune signatures of disease. Together, our cross-species programme aims to uncover biologically grounded treatment targets and to advance a mechanistic understanding of how the brain generates perception and thought.