Fagiolini Michela, Fritschy Jean-Marc, Löw Karin, Möhler Hanns, Rudolph Uwe, Hensch Takao K
Laboratory for Neuronal Circuit Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198 Japan.
Science. 2004 Mar 12;303(5664):1681-3. doi: 10.1126/science.1091032.
Weak inhibition within visual cortex early in life prevents experience-dependent plasticity. Loss of responsiveness to an eye deprived of vision can be initiated prematurely by enhancing gamma-aminobutyric acid (GABA)-mediated transmission with benzodiazepines. Here, we use a mouse "knockin" mutation to alpha subunits that renders individual GABA type A (GABA(A)) receptors insensitive to diazepam to show that a particular inhibitory network controls expression of the critical period. Only alpha1-containing circuits were found to drive cortical plasticity, whereas alpha2-enriched connections separately regulated neuronal firing. This dissociation carries implications for models of brain development and the safe design of benzodiazepines for use in infants.
生命早期视觉皮层内的微弱抑制会阻止经验依赖性可塑性。通过用苯二氮䓬增强γ-氨基丁酸（GABA）介导的传递，可以过早引发对失明眼睛反应性的丧失。在此，我们利用小鼠对α亚基的“敲入”突变，使单个GABA A型（GABA(A)）受体对安定不敏感，以表明特定的抑制性网络控制关键期的表达。仅发现含有α1的回路驱动皮层可塑性，而富含α2的连接分别调节神经元放电。这种分离对脑发育模型以及用于婴儿的苯二氮䓬的安全设计具有启示意义。
