The enhanced cognitive abilities characterizing the human species result from specialized features of neuronal circuits. The evolution of human brain circuits is thought to be linked to species-specific features at the level of individual neurons, including the way they develop, connect, and respond to environmental cues. Still, the links between genomic changes that occurred during evolution and the emergence of humanspecific neuronal properties remain largely unknown. Here we will identify such genomic changes through
single-cell multi-omics and computational modeling of cortical neurons. We will then test their impact in vivo on neuronal development, function, and plasticity. Finally, we will examine how species-specific genomic
changes impact the response of human cortical neurons to extrinsic changes, including environmental stress.
This project will uncover the mechanistic links between genome and neuronal evolution, thereby shedding new light on the evolution of the human brain and its sensitivity to specific diseases.