Neuron
Volume 85, Issue 5, 4 March 2015, Pages 982-997
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Article
Area-Specific Reestablishment of Damaged Circuits in the Adult Cerebral Cortex by Cortical Neurons Derived from Mouse Embryonic Stem Cells

https://doi.org/10.1016/j.neuron.2015.02.001Get rights and content
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Highlights

  • ESC-derived cortical pyramidal neurons engraft in adult mouse lesioned cortex

  • Grafted neurons display long-range patterns of connectivity with the host

  • Transplant-derived patterns of projections are cortical area specific

  • Integration requires a match in the areal identity of grafted and lesioned neurons

Summary

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.

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Present address: Department of Genetics, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA