Decoding cortical interneuron diversity at a single cell level to approach the pathophysiology of interneuropathies
GABAergic inhibitory interneurons falling into at least 20 subpopulations regulate key aspects of functional cortical maturation at various developmental stages and altered cortical inhibition. Developmental defects in the GABAergic system contribute to the pathophysiology of neuropsychiatric disorders like epilepsy, autism and schizophrenia. Thus, deciphering the developmental determinants sculpting the physiological diversity of GABAergic interneurons seems fundamental to understand the logic behind their integration into cortical cell assemblies, as well as causes for cortical dysfunction. Thus, here we aim to apply an elegant single-cell based approach combining the highly innovative high-throughput methods Next Generating Sequencing and Nanostring nCounter technology to comprehensively profile the transcriptional determinants of interneuron subtype specification. The function of identified key players regulating particular interneuron cell fates and development are evaluated including a battery of sensitive bioassays as well as in vivo studies. The superior objective of this proposal is the understanding of the basic neurodevelopmental mechanisms in a disease-relevant background.