Connectivity and function of regenerated neurons in the cerebral cortex – from transplantation to direct neuronal reprogramming
In the previous funding period we have shown the appropriate integration of neurons transplanted from fetal cerebral cortex into the adult murine visual cortex with brain-wide adequate input and output and the acquisition of well-tuned orientation- and direction selective receptive field properties (Falkner, Grade et al., 2016). In the previous study we used an ablation model that targets selectively upper layer neurons. In the present project we aim to further develop the question of new neuron integration into the visual cortex towards more clinically relevant models of traumatic injury in young and old mice. We also aim to compare integration of transplanted neurons to the integration of new neurons obtained by direct reprogramming from local reactive glial cells, as we achieved a breakthrough in the last funding period inducing mature pyramidal neurons with very high efficiency (Gascón, Murenu et al., 2016). We will examine axonal projections of these induced neurons and, in collaboration with B02, the myelination pattern of their axons. Brain-wide monosynaptic input to the induced neurons will be determined as described previously (Falkner, Grade et al., 2016). In our continued collaboration with A08 Ca-imaging will be used to determine the receptive field properties of the induced neurons in vivo also in awake mice.