October 22, 2025

Understanding schizophrenia by bridging mouse and human brain circuits

FMI group leader Prof. Georg Keller and Prof. Philip Sterzer from Universitären Psychiatrischen Kliniken (UPK) Basel have jointly been awarded a Schweizerischer Nationalfonds (SNF) grant over 1.5 million CHF to investigate the brain circuit changes that underlie schizophrenia. Keller and Sterzer’s project aims to bridge a gap between fundamental neuroscience and clinical research — by linking discoveries from mouse models to brain activity patterns in humans.

Schizophrenia affects how people think, feel, and perceive reality. Despite decades of research, the neural mechanisms driving this complex condition remain poorly understood. Keller’s team recently discovered that antipsychotic drugs have a distinctive effect on the brain’s cortex in mice: they reduce synchronized activity among a particular subset of neurons in a layer 5 — a deep layer of the brain cortex. These neurons are thought to play a key role in how the brain processes predictions and errors — functions that are often disrupted in schizophrenia. Read more

The new joint project builds directly on these insights. By combining advanced mouse experiments with brain recordings in humans — using imaging techniques such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) — the team will test whether similar patterns occur in people with schizophrenia and whether disruptions in the layer 5 circuit might contribute to the disease. In later stages, the researchers plan to explore cell-type-specific markers of psychosis, which could reveal new therapeutic targets.

The project will lay the groundwork for future clinical trials that directly test whether schizophrenia involves a malfunction in cortical layer 5 circuits. Ultimately the findings could help to develop new, more effective treatments, especially for symptoms that are still difficult to treat in psychiatry today.