Valdés-Sánchez Lourdes, Escámez Teresa, Echevarria Diego, Ballesta Juan J, Tabarés-Seisdedos Rafael, Reiner Orly, Martinez Salvador, Geijo-Barrientos Emilio
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Campus de San Juan, Apartado 18, San Juan, 03550 Alicante, Spain.
Mol Cell Neurosci. 2007 Jun;35(2):220-9. doi: 10.1016/j.mcn.2007.02.017. Epub 2007 Mar 3.
Mutations in the mouse Lis1 gene produce severe alterations in the developing cortex. We have examined some electrophysiological responses of cortical pyramidal neurons during the early postnatal development of Lis/sLis1 mutant mice. In P7 and P30 Lis1/sLis1 neurons we detected a lower frequency and slower decay phase of mIPSCs, and at P30 the mIPSCs amplitude and the action potential duration were reduced. Zolpidem (an agonist of GABAA receptors containing the alpha1 subunit) neither modified the amplitude nor the decay time of mIPSCs at P7 in Lis1/sLis1 neurons, whereas it increased the decay time at P30. The levels of GABAA receptor alpha1 subunit mRNA were reduced in the Lis1/sLis1 brain at P7 and P30, whereas reduced levels of the corresponding protein were only found at P7. These results demonstrate the presence of functional alterations in the postnatal Lis1/sLis1 cortex and point to abnormalities in GABAA receptor subunit switching processes during postnatal development.
小鼠Lis1基因的突变会使发育中的皮层产生严重改变。我们已经研究了Lis1/sLis1突变小鼠出生后早期发育过程中皮层锥体神经元的一些电生理反应。在出生后第7天（P7）和第30天（P30）的Lis1/sLis1神经元中，我们检测到微小抑制性突触后电流（mIPSCs）的频率较低且衰减期较慢，并且在P30时，mIPSCs的幅度和动作电位持续时间减小。唑吡坦（一种含有α1亚基的GABAA受体激动剂）在P7时既不改变Lis1/sLis1神经元中mIPSCs的幅度，也不改变其衰减时间，而在P30时它增加了衰减时间。在P7和P30时，Lis1/sLis1脑内GABAA受体α1亚基mRNA的水平降低，而相应蛋白质水平仅在P7时降低。这些结果表明出生后Lis1/sLis1皮层存在功能改变，并指出出生后发育过程中GABAA受体亚基转换过程存在异常。
