Neonatal development of the rat visual cortex:: synaptic function of GABAA receptor α subunits
Neonatal development of the rat visual cortex:: synaptic function of GABAA receptor α subunits
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DOI：
10.1113/jphysiol.2002.026534
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发表时间：
2002-11-15
影响因子：
5.5
通讯作者：
Brussaard, AB
中科院分区：
文献类型：
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作者：
Bosman, LWJ;Rosahl, TW;Brussaard, AB
每个GABA(A)受体由两个α和三个其他亚基组成。中枢神经系统表达的不同α亚基异构体的空间和时间分布受到高度调控。在这里，我们研究了不同的阿尔法亚基在新生大鼠视皮质发育过程中功能贡献的变化。首先，我们利用亚基特异性药理学和电生理记录相结合的方法，在急切制备的脑片上表征了突触后II-III层神经元中阿尔法亚基的表达。这表明，在发育过程中，Bretazenil(1um)的作用明显下调，而100 nM的唑吡坦对自发抑制性突触后电流(SIPSCs)的作用明显上调。鉴于使用的浓度，我们将其解释为突触α3的下调和α1亚单位的上调。此外，速尿的作用在出生后6天至21天之间增加，这表明α4的功能贡献。我们的第二个目的是研究α亚基表达的可塑性对GABA能IPSCs衰变特性的影响。我们发现，对Bretazenil敏感的IPSCs在幼年神经元中具有最长的衰变时间常数。在成熟神经元中，对唑吡坦和速尿敏感的IPSCs有相对较快的衰减动力学，而对Bretazenil敏感的IPSCs衰减相对较慢。对α1基因缺陷小鼠和大鼠外植体中α1反义寡核苷酸缺失的分析显示，结果与应用唑吡坦的结果相似。因此，不同的阿尔法亚基贡献在大脑皮层IPSC衰变的发育加速中创造了异质性。
Each GABA(A) receptor consists of two alpha and three other subunits. The spatial and temporal distribution of different alpha subunit isomeres expressed by the CNS is highly regulated. Here we study changes in functional contribution of different alpha subunits during neonatal development in rat visual cortex. First, we characterized postsynaptic alpha subunit expression in layer II-III neurons, using subunit-specific pharmacology combined with electrophysiological recordings in acutely prepared brain slices. This showed clear developmental downregulation of the effects of bretazenil (1 mum) and marked upregulation of the effect of 100 nM of zolpidem on the decay of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the concentrations used we interpret this as downregulation of the synaptic alpha3 and upregulation of alpha1 subunit. Furthermore, the effect of furosemide, being indicative of the functional contribution of alpha4, was increased between postnatal days 6 and 21. Our second aim was to study the effects of plasticity in alpha subunit expression on decay properties of GABAergic IPSCs. We found that bretazenil-sensitive IPSCs have the longest decay time constant in juvenile neurons. In mature neurons, zolpidem- and furosemide-sensitive IPSCs have relatively fast decay kinetics, whereas bretazenil-sensitive IPSCs decay relatively slowly. Analysis of alpha1 deficient mice and alpha1 antisense oligonucleotide deletion in rat explants showed similar results to those obtained by zolpidem application. Thus, distinct alpha subunit contributions create heterogeneity in developmental acceleration of IPSC decay in neocortex.