PIF2024 - LA PLASTICIDAD DURANTE EL DESARROLLO DE LOS CIRCUITOS DE LA CORTEZA CEREBRAL. PROGRAMAS DE DIFERENCIACION NEURONAL CON POTENCIAL PARA EL REJUVENECIMIENTO Y REPARACION - (PID2023-146322NB-I00)

The cerebral cortex is one of the most complex biological structures and its responsible form the high order functions of the human brain. Its improper development underlies severe symptoms and disabilities associated with psychiatric, neurodevelopmental conditions and its malfunction is observed in neurodegeneration and aging. The general goal of the proposal is to investigate the early programs instructing the development of mammalian cortical neurons and the programs that restrict developmental plasticity and block repair in the adult. It investigates rejuvenation/reprogramming strategies to repair the brain. This proposal originates on our previous findings (Bragg-Gonzalo and Aguilera et al., Sci. Adv.10,eadj9911(2024); De León Reyes et al.; Nat. Comms 10, 4549 (2019); Develop 147, (2020); Rodríguez-Tornos et al., Neuron (2016), 89, (3), 494-506.)). It includes three partial objectives: Obj 1) The developmental role of GABAeric interneurons in determining L2/3 PN long-range projections. Obj 2) Cux1 as a terminal identity factor and gatekeeper of molecular plasticity blocking neurodegeneration. Obj 3) Early programs of intracortical specification and reprogramming/rejuvenation strategies. Methodologically, the investigation involves in vivo mouse models, in utero electroporation, cranial injections, RNAseq, axonal tracing, chemogenetics, confocal microscopy, and behavioral tests. The early career investigator will perform an international training stage abroad.