Journal
CEREBRAL CORTEX
Volume 21, Issue 2, Pages 413-424Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhq107
Keywords
glutamatergic neurons; network activity; neural repair; reprogramming; synapse formation
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Funding
- Deutsche Forschungsgemeinschaft [BE4182/1-3, BL567/2-2, GU230/5-3]
- European Union [LSHG-CT-2007-037445]
- Bundesministerium fur Bildung und Forschung
- Bavarian State Ministry of the Sciences, Research, and the Arts
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In the subependymal zone and the dentate gyrus of the adult brain of rodents, neural stem cells with glial properties generate new neurons in a life-long process. The identification of glial progenitors outside the neurogenic niches, oligodendrocyte precursors in the healthy brain, and reactive astrocytes after cortical injury led to the idea of using these cells as endogenous cell source for neural repair in the cerebral cortex. Recently, our group showed that proliferating astroglia from the cerebral cortex can be reprogrammed into neurons capable of action potential firing by forced expression of neurogenic fate determinants but failed to develop synapses. Here, we describe a maturation profile of cultured reprogrammed NG2+ and glial fibrillary acidic protein+ glia cells of the postnatal rat cortex that ends with the establishment of a glutamatergic neuronal network. Within 3 weeks after viral expression of the transcription factor neurogenin 2 (Ngn2), glia-derived neurons exhibit network-driven, glutamate receptor-dependent oscillations in Ca2+ and exhibit functional pre- and postsynaptic specialization. Interestingly, the Ngn2-instructed glutamatergic network also supports the maturation of a g-aminobutyric acid (GABA) ergic input via GABA(A) receptors in a non-cell autonomous manner. The proof-of-principle'' results imply that a single transcription factor may be sufficient to instruct a neuronal network from a glia-like cell source.
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