Lmo4 in the basolateral complex of the amygdala modulates fear learning.
Lmo4 in the basolateral complex of the amygdala modulates fear learning.
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DOI：
10.1371/journal.pone.0034559
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Heberlein U
中科院分区：
文献类型：
--
作者：
Maiya R;Kharazia V;Lasek AW;Heberlein U
巴甫洛夫恐惧条件反射是一种联想学习范式，在这种学习范式中，小鼠学会将中性条件刺激与厌恶的无条件刺激联系起来。在这项研究中，我们展示了转录调节因子LMO4在恐惧学习中的一个新角色。LMO4主要表达于杏仁基底外侧复合体(BLC)的锥体投射神经元。在Lmo4基因座(Lmo4gt/+)杂合的小鼠比它们的野生型(WT)小鼠表达的Lmo4少50%，它们对接受厌恶刺激的背景和线索都表现出更强的冰冻。小发夹RNA介导的LMO4在BLC中的敲除，而不是海马齿状回区域，概括了这种增强的条件表型，表明LMO4在恐惧学习中具有成人和大脑区域特有的作用。免疫组织化学分析显示，恐惧条件作用后，Lmo4gt/+小鼠BLC中c-Fos阳性斑点数较WT小鼠增多。最后，我们使用高架加迷宫、开场和明暗盒测试，测量了Lmo4gt/+小鼠和BLC特异性下调LMO4的小鼠的焦虑样行为。LMO4的全局或BLC特异性敲除对焦虑样行为没有显著影响。这些结果表明，LMO4在调节习得性恐惧而不是未习得性恐惧中起着选择性的作用。
Pavlovian fear conditioning is an associative learning paradigm in which mice learn to associate a neutral conditioned stimulus with an aversive unconditioned stimulus. In this study, we demonstrate a novel role for the transcriptional regulator Lmo4 in fear learning. LMO4 is predominantly expressed in pyramidal projection neurons of the basolateral complex of the amygdala (BLC). Mice heterozygous for a genetrap insertion in the Lmo4 locus (Lmo4gt/+), which express 50% less Lmo4 than their wild type (WT) counterparts display enhanced freezing to both the context and the cue in which they received the aversive stimulus. Small-hairpin RNA-mediated knockdown of Lmo4 in the BLC, but not the dentate gyrus region of the hippocampus recapitulated this enhanced conditioning phenotype, suggesting an adult- and brain region-specific role for Lmo4 in fear learning. Immunohistochemical analyses revealed an increase in the number of c-Fos positive puncta in the BLC of Lmo4gt/+ mice in comparison to their WT counterparts after fear conditioning. Lastly, we measured anxiety-like behavior in Lmo4gt/+ mice and in mice with BLC-specific downregulation of Lmo4 using the elevated plus maze, open field, and light/dark box tests. Global or BLC-specific knockdown of Lmo4 did not significantly affect anxiety-like behavior. These results suggest a selective role for LMO4 in the BLC in modulating learned but not unlearned fear.
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影响因子：
64.5
作者：
BOURTCHULADZE, R;FRENGUELLI, B;SILVA, AJ
通讯作者：
SILVA, AJ
DOI：
10.1111/j.1601-183x.2009.00515.x
发表时间：
2009-11
期刊：
Genes, brain, and behavior
影响因子：
--
作者：
Lamprecht R;Dracheva S;Assoun S;LeDoux JE
通讯作者：
LeDoux JE
影响因子：
5.3
作者：
Kashani, Amir H.;Qiu, Zilong;Ghosh, Anirvan
通讯作者：
Ghosh, Anirvan
影响因子：
4.7
作者：
Heberlein U;Tsai LT;Kapfhamer D;Lasek AW
通讯作者：
Lasek AW
DOI：
10.1073/pnas.0305170101
发表时间：
2004-02-17
影响因子：
11.1
作者：
Hong, SJ;Li, HW;Dawson, TM
通讯作者：
Dawson, TM