Precise Integration of Direct Cell Reprogramming-Induced Neuronal Cells into Adult Neocortical Circuits

Abstract

Recent discovery of in vivo reprogramming of glia cells to neurons by definedneurogenic transcription factors in the adult brain has provided a new approach forneuronal replacement therapy. However, it remains completely unknown whether andhow these direct cell reprogramming-induced neuronal cells (iNs) are functionallyintegrated into the existing neural circuits. We report here that in the adult mouseprimary visual cortex (V1), the iNs, reprogrammed from astrocyte by a singletranscription factor Ascl1, can develop proper distinct visual tuning functions and theyare precisely integrated into the existing retinotopic map, compared to originalcounterparts. Matured iNs receive brain-wide afferent connections that are known toinnervate the V1. They form fully-assembled structures of afferent and efferent synapseswith pre-existing V1 neurons under electron microscopy. Thus, these in vivo findingsstrongly endorse promise for application of direct cell-reprogramming to the neuralcircuit reconstruction in a diseased or injured brain.