ArealPlasticity · Area-specific transcriptional dynamics and plasticity of neocortical neurons

Cellular diversity in the nervous system determines the variety of circuits that set the framework for brain function. These different types of neurons emerge during pre- and post-natal development through the regulation of gene networks by two archetypical processes: cell-intrinsic processes, which are independent of environmental conditions, and cell-extrinsic processes, which are triggered by environmental signals. A continuum of interactions between intrinsic and extrinsic processes underlie cellular states. However, their respective contribution to neuronal identity has been difficult to untangle because neurons are highly interconnected and heterogeneous cell-types with distinct and dynamic sensitivities to environmental signals. Here, using the mouse neocortex as a model system, I will investigate how cell-intrinsic and cell-extrinsic processes interact to define neuronal identities using Patch-seq assessment of neuronal molecular identity following transplantation across cortical areas. Neuronal “plasticity” will be assessed by transplantation, which corresponds to the artificial altering of the environmental factors. Data comparison between transplanted neurons and controls will identify the candidate of “core genes” which regulate the environment-dependent plasticity of neuronal differentiation. Finally, I will manipulate these candidate genes and analyze their effect on final neuronal identity to validate their causal relationship. Altogether, this study will contribute to revealing the plasticity of neuronal identity across cortical areas and to addressing environment-dependent molecular mechanisms controlling the plasticity. In the long term, this may contribute to a better understanding of neurodevelopmental and psychiatric disorders, in which cell-intrinsic and extrinsic factors interact to produce the disease.