Development of inhibitory circuits in the human cerebral cortex

The extraordinary diversity of animal behaviours relies on the precise assembly and fine-tuning of synapses in the brain. This connectivity reaches an exceptional level of complexity in the mammalian cerebral cortex, where the remarkable diversity of interneurons enables them to influence pyramidal cells in many ways and increase their computation power. Human behaviour remains unparalleled in scope and sophistication compared to other species. While we understand the principal rules underlying the development of cortical circuits in other species, how this complexity emerges in humans is unknown. Our central hypothesis is that human inhibitory circuitries may use universal and specific molecular codes compared to other species. This proposal aims to investigate the mechanisms through which cortical circuitries, including interneuron connectivity, develop in humans. We will use cutting-edge technology, from scRNAseq, xenotransplantation of human stem cells, and ex-vivo human slice culture, to explore how the interneurons assemble their synapses. This is highly relevant since increasing evidence suggests that impaired neuronal circuit development in the cerebral cortex constitutes the biological basis for some of the most devastating human disorders, such as autism or schizophrenia.