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Blum, R.* ; Heinrich, C.* ; Sánchez, R.* ; Lepier, A.* ; Gundelfinger, E.D.* ; Berninger, B.* ; Götz, M.

Neuronal network formation from reprogrammed early postnatal rat cortical glial cells.

Cereb. Cortex 21, 413-424 (2011)
Publ. Version/Full Text Volltext DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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 Ca(2+) and exhibit functional pre- and postsynaptic specialization. Interestingly, the Ngn2-instructed glutamatergic network also supports the maturation of a gamma-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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Gutamatergic neurons; Network activity; Neural repair; Reprogramming; Synapse formation
ISSN (print) / ISBN 1047-3211
e-ISSN 1460-2199
Journal Cerebral Cortex
Quellenangaben Volume: 21, Issue: 2, Pages: 413-424 Article Number: , Supplement: ,
Publisher Oxford University Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)