Mice lacking the major adult GABAA receptor subtype have normal number of synapses, but retain juvenile IPSC kinetics until adulthood
Mice lacking the major adult GABAA receptor subtype have normal number of synapses, but retain juvenile IPSC kinetics until adulthood
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DOI：
10.1152/jn.00084.2005
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发表时间：
2005-07-01
影响因子：
2.5
通讯作者：
Brussaard, AB
中科院分区：
文献类型：
--
作者：
Bosman, LWJ;Heinen, K;Brussaard, AB
在结构和功能上不同的GABA(A)受体亚型有很大的差异。GABA(A)受体亚单位的表达模式受到高度调控，无论是暂时的还是空间的。特别是在发育过程中，亚基的表达发生了深刻的变化。在大多数脑区，GABA(A)受体α1亚基取代α2和/或α3亚基成为主要的α亚基。伴随而来的是GABA(A)受体开放时间的显著缩短以及突触后反应的持续时间。我们在这里描述了在缺乏α1亚单位的小鼠中GABA能突触传递的发展。我们表明，阿尔法1在很大程度上--但不完全--是发育中和成熟大脑中突触后反应持续时间相对较短的原因。然而，当α1仅少量表达时，它已经影响了新生儿大脑皮层中的GABA能传递。似乎阿尔法1/-小鼠并没有表现出GABA能突触的大幅减少，但确实在成年后保留了长时间的突触后电流。因此，它们形成了一个很好的模型来研究发育中GABA(A)受体亚单位转换的功能作用。
There is a large variation in structurally and functionally different GABA(A) receptor subtypes. The expression pattern of GABA(A) receptor subunits is highly regulated, both temporarily and spatially. Especially during development, profound changes in subunit expression have been described. In most brain areas, the GABA(A) receptor alpha 1 subunit replaces the alpha 2 and/or alpha 3 subunit as major alpha subunit. This is accompanied by a marked decrease in the open time of GABA(A) receptors and hence in the duration of postsynaptic responses. We describe here the development of GABAergic, synaptic transmission in mice lacking the alpha 1 subunit. We show that alpha 1 is to a large extent-but not entirely-responsible for the relatively short duration of postsynaptic responses in the developing and the mature brain. However, alpha 1 already affects GABAergic transmission in the neonatal cerebral cortex when it is only sparsely expressed. It appears that the alpha 1 -/- mice do not show a large reduction in GABAergic synapses but do retain long-lasting postsynaptic currents into adulthood. Hence, they form a good model to study the functional role of developmental GABA(A) receptor subunit switching.