The LIM homeodomain protein Lhx6 regulates maturation of interneurons and network excitability in the mammalian cortex.
The LIM homeodomain protein Lhx6 regulates maturation of interneurons and network excitability in the mammalian cortex.
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DOI：
10.1093/cercor/bhs159
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发表时间：
2013-08
期刊：
影响因子：
--
通讯作者：
Pachnis V
中科院分区：
文献类型：
--
作者：
Neves G;Shah MM;Liodis P;Achimastou A;Denaxa M;Roalfe G;Sesay A;Walker MC;Pachnis V
LIM同源结构域转录因子编码Lhx6基因在小鼠中的缺失导致皮质中间神经元的缺陷性切向迁移和生长抑素（Sst）和小清蛋白（Pva）表达亚型的分化失败。在这里，我们描述了一种新的亚纯型等位基因Lhx6，并表明，该位点的活动减少导致广泛的分化缺陷Sst+ interneurons，但相对较小的和本地化的变化Pva+ interneurons。Sst表达细胞数量的减少与中间神经元的损失无关，因为Lhx6表达的中间神经元的迁移和数量以及特征性分子标记物（如钙蛋白或神经肽Y）的表达在Lhx6低形态小鼠中不受影响。在海马CA1区的Sst+ interneurons分化的选择性缺陷相一致，我们观察到的层oriens和树突状抑制的特征性变化的代谢型谷氨酸受体1的表达减少，但正常的抑制输入到体细胞室的CA1锥体细胞。此外，Lhx6亚型显示从成年早期开始的反复发作活动的行为、组织学和脑电图体征。这些结果表明Lhx6在哺乳动物皮层中皮层中间神经元的成熟和抑制回路的形成中起重要作用。
Deletion of LIM homeodomain transcription factor-encoding Lhx6 gene in mice results in defective tangential migration of cortical interneurons and failure of differentiation of the somatostatin (Sst)- and parvalbumin (Pva)-expressing subtypes. Here, we characterize a novel hypomorphic allele of Lhx6 and demonstrate that reduced activity of this locus leads to widespread differentiation defects in Sst+ interneurons, but relatively minor and localized changes in Pva+ interneurons. The reduction in the number of Sst-expressing cells was not associated with a loss of interneurons, because the migration and number of Lhx6-expressing interneurons and expression of characteristic molecular markers, such as calretinin or Neuropeptide Y, were not affected in Lhx6 hypomorphic mice. Consistent with a selective deficit in the differentiation of Sst+ interneurons in the CA1 subfield of the hippocampus, we observed reduced expression of metabotropic Glutamate Receptor 1 in the stratum oriens and characteristic changes in dendritic inhibition, but normal inhibitory input onto the somatic compartment of CA1 pyramidal cells. Moreover, Lhx6 hypomorphs show behavioral, histological, and electroencephalographic signs of recurrent seizure activity, starting from early adulthood. These results demonstrate that Lhx6 plays an important role in the maturation of cortical interneurons and the formation of inhibitory circuits in the mammalian cortex.
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影响因子：
3.7
作者：
Ali, Afia B.;Thomson, Alex M.
通讯作者：
Thomson, Alex M.
影响因子：
5.3
作者：
Borges, K;Gearing, M;Dingledine, R
通讯作者：
Dingledine, R
DOI：
10.1523/jneurosci.1531-09.2009
发表时间：
2009-09-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Huang Z;Walker MC;Shah MM
通讯作者：
Shah MM
影响因子：
34.7
作者：
Ascoli, Giorgio A.;Alonso-Nanclares, Lidia;Anderson, Stewart A.;Barrionuevo, German;Benavides-Piccione, Ruth;Burkhalter, Andreas;Buzsaki, Gyoergy;Cauli, Bruno;DeFelipe, Javier;Fairen, Alfonso;Feldmeyer, Dirk;Fishell, Gord;Fregnac, Yves;Freund, Tamas F.;Gardner, Daniel;Gardner, Esther P.;Goldberg, Jesse H.;Helmstaedter, Moritz;Hestrin, Shaul;Karube, Fuyuki;Kisvarday, Zoltan F.;Lambolez, Bertrand;Lewis, David A.;Marin, Oscar;Markram, Henry;Munoz, Alberto;Packer, Adam;Petersen, Carl C. H.;Rockland, Kathleen S.;Rossier, Jean;Rudy, Bernardo;Somogyi, Peter;Staiger, Jochen F.;Tamas, Gabor;Thomson, Alex M.;Toledo-Rodriguez, Maria;Wang, Yun;West, David C.;Yuste, Rafael
通讯作者：
Yuste, Rafael
影响因子：
16.2
作者：
Monory, Krisztina;Massa, Federico;Lutz, Beat
通讯作者：
Lutz, Beat