Investigating the effect of maternal inflammation on cortical inhibitory neuron development using 3D human brain cultures: Implications in Autism spec

The developing brain is sensitive to various environmental factors that can increase the probability of neurodevelopmental disorders. One such factor is maternal immune activation (MIA), which can be triggered by infections or disease during pregnancy, and significantly increase the likelihood of offspring developing autism spectrum disorder (ASD). An underlying mechanism of ASD and other neurodevelopmental disorders is an imbalance in neuronal excitation and inhibition (E/I) in the brain. Animal studies have revealed that MIA disrupts the generation of inhibitory cortical GABAergic interneurons, a specific cell type strongly associated with ASD. Unlike excitatory neurons, interneurons do not originate directly in the cortex but instead emerge from neural stem cells located in the ganglionic eminences. Subsequently, their progenies undergo tangential migration over substantial distances during fetal brain development, navigating complex pathways to reach their final destinations within the cortex. However, due to the limited availability of model systems for investigating human inhibitory neuron development, the intricate cellular and molecular mechanisms by which MIA influences various stages of inhibitory neuron development and subsequent E/I imbalance remain unknown.
This project will to establish a 3D culturing system of human ganglionic eminence tissue to investigate how MIA affects the development of cortical GABAergic interneurons.