Understanding the role of microglia in psychiatric disorders is currently the main focus of our lab. Microglia are the main population of immune cells in the brain parenchyma. Microglia are known for regulating inflammation in the central nervous system. However, it is becoming more and more clear that these cells play also crucial roles when there is no inflammation. Microglia are important for shaping neuronal connections and regulation of neuronal functioning. Since altered neuronal connections and functioning is thought to underlie psychiatric disorders, dysfunction of microglia while performing these roles is hypothesized to contribute. We have set up several tools to study and characterize human microglia in health and pathology. We characterize their density and morphology in specific cortical layers (Figure 1) and we isolate them from post-mortem brain tissue for further characterization of the cells (Figure 2). The last years we have successfully isolated and characterized microglia from different brain regions from more >120 donors. These samples are used to investigate disease-related changes in microglia phenotype and function, as well as to analyze how genetic risk for neuropsychiatric disorder is related to gene expression (Figure 2). For further in-depth studies on changes in microglia function, in vitro cell models are needed. In our lab we have used advances of recent developments to culture microglia from monocytes and iPSCs and to generate cerebral organoids (Video and figure 3). We have optimized these models and with our colleagues in Utrecht the Netherlands, we were the first lab to describe a human cerebral organoid model in which microglia develop together with astrocytes and neurons. We use these models to study how genetic and environmental risk factors for psychiatric disorders change the phenotype and function of microglia and non-microglia cell types.