Tang Yunshuo, Stryker Michael P, Alvarez-Buylla Arturo, Espinosa Juan Sebastian
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
Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):18339-44. doi: 10.1073/pnas.1421844112. Epub 2014 Dec 8.
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.
γ-氨基丁酸能抑制作用已被证明在大脑可塑性关键期的开启中发挥重要作用。我们最近发现，移植来自胚胎内侧神经节隆起（MGE）的γ-氨基丁酸能前体细胞，即新皮质小白蛋白阳性（PV(+)）和生长抑素表达阳性（SST(+)）中间神经元的来源，可以在内源性关键期关闭后诱导新的眼优势可塑性（ODP）时期。在γ-氨基丁酸能中间神经元的多种亚型中，PV(+)细胞被认为在ODP中起关键作用。在这里，我们使用携带白喉毒素α亚基条件等位基因和细胞特异性表达Cre重组酶的MGE移植来选择性地耗尽PV(+)或SST(+)中间神经元，并研究每种类型的中间神经元对ODP的贡献。正如预期的那样，在含有PV(+)细胞但大多数SST(+)中间神经元被耗尽的移植中观察到了强大的可塑性。令人惊讶的是，大多数PV(+)细胞被耗尽的移植诱导可塑性的效果与含有PV(+)细胞的移植一样有效。相比之下，耗尽这两种细胞类型会阻止可塑性的诱导。这些发现表明，PV(+)细胞在ODP中并不起唯一作用；SST(+)中间神经元也可以驱动皮质可塑性并有助于神经网络的重塑。PV(+)和SST(+)中间神经元诱导从头开始的皮质可塑性的能力可能有助于开发新的脑修复治疗方法。
