Regulation of gephyrin and GABAA receptor binding within the amygdala after fear acquisition and extinction
Regulation of gephyrin and GABAA receptor binding within the amygdala after fear acquisition and extinction
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DOI：
10.1523/jneurosci.3301-04.2005
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发表时间：
2005-01-12
影响因子：
5.3
通讯作者：
Davis, M
中科院分区：
文献类型：
--
作者：
Chhatwal, JP;Myers, KM;Davis, M
条件性恐惧的获得和消除似乎都需要基底外侧杏仁核（BLA）。由于这两种形式的学习对条条性恐惧的表达有相反的影响，我们假设它们可能在BLA内调节gaba能张力的差异。先前，我们报道了GABA(A)受体聚类蛋白gephyrin的基因表达在恐惧习得后显著下调（Ressler et al., 2002）。在这里，我们证明了类似的BLA卟啉蛋白水平的下降，以及恐惧习得后BLA中GABA(a)受体表面表达的下降，这可以通过h3 -氟西泮的结合减少来证明。与此形成鲜明对比的是，消光训练后，BLA中gephyrin mRNA和蛋白水平显著升高，h3 -氟硝西泮结合也显著升高。这些结果暗示了gephyrin蛋白在恐惧习得和恐惧消退中都起作用，并提示BLA中gephyrin和GABA(A)受体表达的调节可能在这两种学习类型的经验依赖可塑性中起作用。此外，这些结果表明，gaba能突触的生理相关的动态改变发生在bla依赖性学习的巩固阶段，并可能与先前描述的谷氨酸能传递的改变相互作用，以启动和稳定体内记忆的形成。
Both the acquisition and extinction of conditioned fear appear to require the basolateral amygdala (BLA). Because these two forms of learning have opposing effects on the expression of conditioned fear, we hypothesized that they may modulate GABAergic tone differentially within the BLA. Previously, we reported that gene expression for the GABA(A) receptor clustering protein gephyrin was significantly downregulated in the BLA after fear acquisition (Ressler et al., 2002). Here we demonstrate an analogous decrease in BLA gephyrin protein levels, together with a decrease in the surface expression of GABA(A) receptors in the BLA after fear acquisition, as evidenced by decreased binding of H3-flunitrazepam. In marked contrast, gephyrin mRNA and protein levels in the BLA significantly increased after extinction training, as did H3-flunitrazepam binding. These results implicate the protein gephyrin in both fear acquisition and extinction and suggest that the modulation of gephyrin and GABA(A) receptor expression in the BLA may play a role in the experience-dependent plasticity underlying both of these types of learning. Furthermore, these results demonstrate that physiologically relevant, dynamic alterations of GABAergic synapses occur during the consolidation phase of BLA-dependent learning and may interact with previously described alterations in glutamatergic transmission to initiate and stabilize memory formation in vivo.