[en] Pluripotent stem-cell-derived neurons constitute an attractive source for replacement therapies, but their utility remains unclear for cortical diseases. Here, we show that neurons of visual cortex identity, differentiated in vitro from mouse embryonic stem cells (ESCs), can be transplanted successfully following a lesion of the adult mouse visual cortex. Reestablishment of the damaged pathways included long-range and reciprocal axonal projections and synaptic connections with targets of the damaged cortex. Electrophysiological recordings revealed that some grafted neurons were functional and responsive to visual stimuli. No significant integration was observed following grafting of the same neurons in motor cortex, or transplantation of embryonic motor cortex in visual cortex, indicating that successful transplantation required a match in the areal identity of grafted and lesioned neurons. These findings demonstrate that transplantation of mouse ESC-derived neurons of appropriate cortical areal identity can contribute to the reconstruction of an adult damaged cortical circuit.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Michelsen, KA; Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium > Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM)
Acosta-Verdugo, S; Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium > Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM)
Benoit-Marand, M; University of Poitiers, Poitiers Cedex, France > Experimental and Clinical Neurosciences Laboratory, Cellular Therapies in Brain Diseases Group
Espuny Camacho, Ira Mercedes ; Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium > Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM)
Gaspard, N; Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium > Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM)
Saha, B; University of Poitiers, Poitiers Cedex, France > Experimental and Clinical Neurosciences Laboratory, Cellular Therapies in Brain Diseases Group
Gaillard, A; University of Poitiers, Poitiers Cedex, France > Experimental and Clinical Neurosciences Laboratory, Cellular Therapies in Brain Diseases Group
Vanderhaeghen, P; Université Libre de Bruxelles (ULB), 1070 Brussels, Belgium > Institut de Recherches en Biologie Humaine et Moléculaire (IRIBHM)
Language :
English
Title :
Area-specific reestablishment of damaged circuits in the adult cerebral cortex by cortical neurons derived from mouse embryonic stem cells
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