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Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):18339-44. doi: 10.1073/pnas.1421844112. Epub 2014 Dec 8.

Cortical plasticity induced by transplantation of embryonic somatostatin or parvalbumin interneurons.

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Medical Scientist Training Program and Biomedical Sciences Graduate Program, Departments of Neurological Surgery, The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research.
Center for Integrative Neuroscience, and Physiology, and Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94143
Departments of Neurological Surgery, The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research,


GABAergic inhibition has been shown to play an important role in the opening of critical periods of brain plasticity. We recently have shown that transplantation of GABAergic precursors from the embryonic medial ganglionic eminence (MGE), the source of neocortical parvalbumin- (PV(+)) and somatostatin-expressing (SST(+)) interneurons, can induce a new period of ocular dominance plasticity (ODP) after the endogenous period has closed. Among the diverse subtypes of GABAergic interneurons PV(+) cells have been thought to play the crucial role in ODP. Here we have used MGE transplantation carrying a conditional allele of diphtheria toxin alpha subunit and cell-specific expression of Cre recombinase to deplete PV(+) or SST(+) interneurons selectively and to investigate the contributions of each of these types of interneurons to ODP. As expected, robust plasticity was observed in transplants containing PV(+) cells but in which the majority of SST(+) interneurons were depleted. Surprisingly, transplants in which the majority of PV(+) cells were depleted induced plasticity as effectively as those containing PV(+) cells. In contrast, depleting both cell types blocked induction of plasticity. These findings reveal that PV(+) cells do not play an exclusive role in ODP; SST(+) interneurons also can drive cortical plasticity and contribute to the reshaping of neural networks. The ability of both PV(+) and SST(+) interneurons to induce de novo cortical plasticity could help develop new therapeutic approaches for brain repair.


critical period; medial ganglionic eminence; ocular dominance plasticity; parvalbumin interneuron; somatostatin interneuron

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