Distinct functional characteristics of the lateral/basolateral amygdala GABAergic system in C57BL/6J and DBA/2J mice
Distinct functional characteristics of the lateral/basolateral amygdala GABAergic system in C57BL/6J and DBA/2J mice
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DOI：
10.1124/jpet.105.100552
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发表时间：
2006-08-01
影响因子：
3.5
通讯作者：
McCool, Brian A.
中科院分区：
文献类型：
--
作者：
DuBois, Dustin W.;Perlegas, Andreas;McCool, Brian A.
一般认为，遗传机制有助于病理性焦虑，C57 BL/6（B6）和DBA/2 J（D2）小鼠，近交系在其焦虑样行为上明显不同，可能代表了研究这些贡献的模型系统。由于外侧/基底外侧杏仁核（BLA）GABA A受体有助于调节焦虑样行为，我们已经测试了这一假设，即受体功能/表达的差异可能与实验测量的焦虑中的应变特异性差异有关。首先，我们证明了在两个单独的测定中焦虑样行为在D2小鼠中更显著。然后，使用分离的神经元的全细胞电生理学，我们发现，D2 BLA神经元比B6 BLA神经元表达显着更大的GABA门控反应。这对GABA A受体是特异性的，因为菌株之间的N-甲基-D-天冬氨酸门控反应相似。在分子水平上，这种增加的GABA A功能与D2 BLA中更高水平的α（2）亚基mRNA表达相关。最后，为了了解这些功能和分子生物学差异的后果，我们研究了电诱发的GABA能反应和自发突触电流，使用体外切片制备的全细胞记录。与B6切片相比，D2切片中的突触前GABA能功能更强大。总之，我们的研究结果表明，在这两种近交系小鼠品系中差异表现的遗传机制导致杏仁核GABA能功能的突触前和突触后方面的显著差异。
It is generally understood that genetic mechanisms contribute to pathological anxiety and that C57BL/6 (B6) and DBA/2J (D2) mice, inbred strains differing markedly in their anxiety-like behaviors, may represent a model system to study these contributions. Because lateral/basolateral amygdala (BLA) GABA A receptors help regulate anxiety-like behaviors, we have tested the hypothesis that differences in receptor function/expression may be related to strain-specific differences in experimentally measured anxiety. First, we demonstrated that anxiety-like behaviors in two separate assays were more substantial in D2 mice. Then, using whole-cell electrophysiology of isolated neurons, we found that D2 BLA neurons expressed significantly greater GABA-gated responses than B6 BLA neurons. This was specific for GABA A receptors, because N-methyl-D-aspartate-gated responses were similar between strains. At the molecular level, this increased GABA A function was associated with higher levels of alpha(2) subunit mRNA expression in D2 BLA. Finally, to understand the ramifications of these functional and molecular biological differences, we examined both electrically evoked GABAergic responses and spontaneous synaptic currents using whole-cell recordings with in vitro slice preparations. Presynaptic GABAergic function was more robust in D2 compared with B6 slices. Together, our findings suggest that genetic mechanisms differentially represented in these two inbred mouse strains lead to robust differences in pre- and postsynaptic aspects of amygdala GABAergic function.