Neuroscience Institute, Georgia State University, Atlanta, Georgia 30302, USA.
Learn Mem. 2010 Feb 13;17(2):109-16. doi: 10.1101/lm.1633710. Print 2010 Feb.
We examined the roles of the amygdala and hippocampus in the formation of emotionally relevant memories using an ethological model of conditioned fear termed conditioned defeat (CD). Temporary inactivation of the ventral, but not dorsal hippocampus (VH, DH, respectively) using muscimol disrupted the acquisition of CD, whereas pretraining VH infusions of anisomycin, a protein synthesis inhibitor, failed to block CD. To test for a functional connection between the VH and basolateral amygdala (BLA), we used a classic functional connectivity design wherein injections are made unilaterally in brain areas either on the same or opposite sides of the brain. A functional connection between the BLA and VH necessary for the acquisition of CD could not be found because unilateral inactivation of either BLA alone (but not either VH alone) was sufficient to disrupt CD. This finding suggested instead that there may be a critical functional connection between the left and right BLA. In our final experiment, we infused muscimol unilaterally in the BLA and assessed Fos immunoreactivity on the contralateral side following exposure to social defeat. Inactivation of either BLA significantly reduced defeat-induced Fos immunoreactivity in the contralateral BLA. These experiments demonstrate for the first time that whereas the VH is necessary for the acquisition of CD, it does not appear to mediate the plastic changes underlying CD. There also appears to be a critical interaction between the two BLAs such that bilateral activation of this brain area must occur in order to support fear learning in this model, a finding that is unprecedented to date.
我们使用一种称为条件性失败（CD）的条件性恐惧的行为学模型，研究了杏仁核和海马体在形成与情绪相关的记忆中的作用。使用 muscimol 暂时抑制腹侧海马体（VH），而不是背侧海马体（DH）的活性，会破坏 CD 的获得，而在预训练时将anisomycin（一种蛋白质合成抑制剂）注入 VH 并不能阻止 CD 的形成。为了测试 VH 和基底外侧杏仁核（BLA）之间的功能连接，我们使用了一种经典的功能连接设计，其中在大脑的同侧或对侧的脑区进行单侧注射。由于单独单侧抑制 BLA（而不是单独单侧抑制 VH）就足以破坏 CD，因此无法找到对于 CD 的获得来说，BLA 和 VH 之间的功能连接。这一发现表明，左右 BLA 之间可能存在关键的功能连接。在我们的最后一个实验中，我们在 BLA 单侧注射 muscimol，并在暴露于社交挫败后评估对侧的 Fos 免疫反应性。单侧抑制 BLA 会显著降低对侧 BLA 中的挫败诱导的 Fos 免疫反应性。这些实验首次表明，虽然 VH 对于 CD 的获得是必要的，但它似乎并不介导 CD 所必需的可塑性变化。此外，两个 BLA 之间似乎存在关键的相互作用，即必须激活这个脑区的双侧，才能在该模型中支持恐惧学习，这一发现是迄今为止前所未有的。
