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首页> 外文期刊>The European Journal of Neuroscience >Alteration of GABAergic synapses and gephyrin clusters in the thalamic reticular nucleus of GABAA receptor alpha3 subunit-null mice.
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Alteration of GABAergic synapses and gephyrin clusters in the thalamic reticular nucleus of GABAA receptor alpha3 subunit-null mice.

机译：GABAA受体α3亚基无效小鼠的丘脑网状核中GABA能突触和gephyrin簇的变化。

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摘要

Multiple GABAA-receptor subtypes are assembled from alpha, beta and gamma subunit variants. GABAA receptors containing the alpha3 subunit represent a minor population with a restricted distribution in the CNS. In addition, they predominate in monoaminergic neurons and in the nucleus reticularis thalami (nRT), suggesting a role in the regulation of cortical function and sleep. Mice with a targeted deletion of the alpha3 subunit gene (alpha3(0/0)) are viable and exhibit a subtle behavioural phenotype possibly related to dopaminergic hyperfunction. Here, we investigated immunohistochemically the consequences of the loss of alpha3 subunit for maturation of GABAA receptors and formation of GABAergic synapses in the nRT. Throughout postnatal development, the regional distribution of the alpha1, alpha2, or alpha5 subunit was unaltered in alpha3(0/0) mice and the prominent alpha3 subunit staining of nRT neurons in wildtype mice was not replaced. Subcellularly, as seen by double immunofluorescence, the alpha3 and gamma2 subunit were clustered at postsynaptic sites in the nRT of adult wildtype mice along with the scaffolding protein gephyrin. In alpha3(0/0) mice, gamma2 subunit clustering was disrupted and gephyrin formed large aggregates localized at the cell surface, but unrelated to postsynaptic sites, indicating that nRT neurons lack postsynaptic GABAA receptors in mutant mice. Furthermore, GABAergic terminals were enlarged and reduced in number, suggesting a partial deficit of GABAergic synapses. Therefore, GABAA receptors are required for gephyrin clustering and long-term synapse maintenance. The absence of GABAA-mediated transmission in the nRT may have a significant impact on the function of the thalamo-cortical loop of alpha3(0/0) mice.
机译：多种GABAA受体亚型由α，β和γ亚基变体组成。含有alpha3亚基的GABAA受体代表少数群体，在CNS中的分布受到限制。此外，它们在单胺能神经元和网状脑丘脑核（nRT）中占主导地位，表明在调节皮层功能和睡眠中起作用。有针对性地删除alpha3亚基基因（alpha3（0/0））的小鼠是可行的，并表现出可能与多巴胺能亢进有关的微妙的行为表型。在这里，我们免疫组化研究了nRT中α3亚基缺失对GABAA受体成熟和GABA能突触形成的影响。在整个产后发育过程中，alpha1，alpha2或alpha5亚基的区域分布在alpha3（0/0）小鼠中没有改变，并且野生型小鼠中nRT神经元的显着alpha3亚基染色没有被替换。如通过双重免疫荧光所见，在亚细胞中，α3和γ2亚基与支架蛋白gephyrin一起聚集在成年野生型小鼠的nRT中的突触后位点。在alpha3（0/0）小鼠中，γ2亚基簇被破坏，gephyrin形成了位于细胞表面的大聚集体，但与突触后位点无关，这表明nRT神经元在突变小鼠中缺乏突触后GABAA受体。此外，GABA能突触的末端增加和减少，表明GABA能突触部分缺失。因此，GABAA受体是gephyrin聚集和长期突触维持所必需的。 nRT中不存在GABA A介导的传递可能对alpha3（0/0）小鼠的丘脑-皮质环的功能产生重大影响。

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