Bilateral phosphorylation of ERK in the lateral and centrolateral amygdala during unilateral storage of fear memories.
Bilateral phosphorylation of ERK in the lateral and centrolateral amygdala during unilateral storage of fear memories.
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DOI：
10.1016/j.neuroscience.2009.08.071
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发表时间：
2009-12-15
期刊：
影响因子：
3.3
通讯作者：
Blair, H. T.
中科院分区：
文献类型：
--
作者：
Tarpley, J. W.;Shlifer, I. G.;Birnbaum, M. S.;Halladay, L. R.;Blair, H. T.
我们之前表明，当通过将听觉条件刺激（CS）与对眼睑的轻微单侧电击（无条件刺激，或US）配对来训练大鼠害怕听觉条件刺激（CS）时，条件冻结取决于对侧杏仁核，而不是来自US的同侧杏仁核。有人提出，CS 和 US 对杏仁核神经元的汇聚激活主要发生在 US 分娩的对侧杏仁核中，导致 CS-US 关联的记忆主要由该半球存储。在本研究中，我们通过在 CS-US 配对之前单侧输注 U0126（在 50% DMSO 载体中）来阻断杏仁核中细胞外信号响应激酶 (ERK) 的磷酸化，进一步测试了这种解释。训练后 24 小时，当 U0126 从美国注射到对侧（而非同侧）时，条件性冻结就会受损，这表明恐惧记忆主要是通过对侧杏仁核巩固的。然而，免疫染色实验表明，在配对（但不是不配对）CS 和 US 呈现后，杏仁核外侧 (LA) 和中央外侧 (CeL) 核的两个半球的 ERK 磷酸化均升高。因此，恐惧获得会诱导杏仁核双侧 ERK 磷酸化，尽管同侧半球似乎没有参与条件冻结。这些发现表明，即使只有一个半球参与冻结行为，两个杏仁核半球也可能发生联想可塑性。条件诱导的 ERK 磷酸化在 LA 的两个半球中是相同的，但在 CeL 的对侧略高于同侧半球。因此，CeL 中可塑性的不对称诱导可能有助于解释为什么在我们的恐惧条件范式中条件冻结优先依赖于来自美国的杏仁核对侧。
We previously showed that when rats were trained to fear an auditory conditioned stimulus (CS) by pairing it with a mild unilateral shock to the eyelid (the unconditioned stimulus, or US), conditioned freezing depended upon the amygdala contralateral but not ipsilateral from the US. It was proposed that convergent activation of amygdala neurons by the CS and US occurred mainly in the amygdala contralateral from US delivery, causing memories of the CS-US association to be stored primarily by that hemisphere. In the present study, we further tested this interpretation by administering unilateral infusions of U0126 (in 50% DMSO vehicle) to block phosphorylation of extracellullar signal-responsive kinase (ERK) in the amygdala prior to CS-US pairings. Conditioned freezing was impaired 24 h after training when U0126 was infused contralaterally—but not ipsilaterally—from the US, suggesting that fear memories were consolidated mainly by the contralateral amygdala. However, immunostaining experiments revealed that ERK phosphorylation was elevated in both hemispheres of the amygdala's lateral (LA) and centrolateral (CeL) nuclei after paired (but not unpaired) presentations of the CS and US. Thus, fear acquisition induced ERK phosphorylation bilaterally in the amygdala, even though the ipsilateral hemisphere did not appear to participate in conditioned freezing. These findings suggest that associative plasticity may occur in both amygdala hemispheres even when only one hemisphere is involved in freezing behavior. Conditioning-induced ERK phosphorylation was identical in both hemispheres of LA, but was slightly greater in the contralateral than ipsilateral hemisphere of CeL. Hence, asymmetric induction of plasticity in CeL might help to explain why conditioned freezing depends preferentially upon the amygdala contralateral from the US in our fear conditioning paradigm.
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