Funktionelle in vivo Restoration genetisch bedingter epileptischer neokortikaler Netzwerke.

01.04.2021 bis 31.03.2024

Most neurodevelopmental, neurodegenerative and some acquired CNS diseases are characterized by functional alterations or loss of specific neuron subpopulations resulting in dysfunctional brain circuits. One neuroregenerative approach is to replenish and reform defective circuitry by transplantation of exogenous neurons. A complementary strategy is to restore circuit dysfunction through functional modulation of endogenous neurons.
We will investigate whether neocortical circuitry can be sufficiently modulated and restored by chemogenetic manipulation of intrinsic neurons and by transplantation of appropriate neuron subtypes. Analysis will be extended toward the question whether restorative approaches applied at incrementally more mature stages and beyond the relatively plastic early postnatal phase could impart organism-level rescue.
Taking advantage of a recently optimized human cortical slice culture model we will finally perform proof-of-concept experiments to approach the question whether chemogenetic and transplantation mediated modulation may be translatable to adult human cortical circuitry.