Fear conditioning induces distinct patterns of gene expression in lateral amygdala.
Fear conditioning induces distinct patterns of gene expression in lateral amygdala.
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DOI：
10.1111/j.1601-183x.2009.00515.x
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
LeDoux JE
中科院分区：
文献类型：
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作者：
Lamprecht R;Dracheva S;Assoun S;LeDoux JE
杏仁核外侧核（LA）通过恐惧条件反射参与与危险相关的刺激的长期联想记忆（LTM）的形成。目前的研究旨在检测相关恐惧条件反射后LA中表达的基因。使用寡核苷酸微阵列，我们监测基因表达的大鼠进行配对训练的音调共同终止与footshock，或不成对的训练的音调和footshock是在一个非重叠的方式。配对的协议始终导致听觉恐惧条件记忆的形成，而非配对的不。当训练后5小时配对组与未配对组相比时，配对组中编码边缘系统相关膜蛋白（Lsamp）、驱动蛋白重链成员2（Kif 2）、N-乙基马来酰亚胺敏感融合蛋白（NSF）和海马钙蛋白样4蛋白（Hpcal 4）的基因表达更高。这些基因编码调节神经元轴突形态（Lsamp、Kif 2）、突触前囊泡循环和释放（Hpcal 4和NSF）以及突触中AMPA受体维持（NSF）的蛋白质。定量实时PCR（qPCR）显示，Kif 2和Lsamp表达小时后恐惧条件反射，但分钟后不成对的训练。Hpcal 4仅在训练后5小时通过配对刺激诱导。这些结果表明，恐惧条件反射诱导一个独特的时间激活的分子通路参与调节突触传递和轴突形态在LA，这是不同的非联想刺激。
The lateral nucleus of the amygdala (LA) has been implicated in the formation of long-term associative memory (LTM) of stimuli associated with danger through fear conditioning. The current study aims to detect genes that are expressed in LA following associative fear conditioning. Using oligonucleotide microarrays, we monitored gene expression in rats subjected to paired training where a tone co-terminates with a footshock, or unpaired training where the tone and footshock are presented in a non-overlapping manner. The paired protocol consistently leads to auditory fear conditioning memory formation whereas the unpaired do not. When the paired group was compared to the unpaired group 5 hrs after training, the expression of genes coding for the limbic system-associated membrane protein (Lsamp), kinesin heavy chain member 2 (Kif2), N-ethylmaleimide sensitive fusion protein (NSF) and Hippocalcin-like 4 protein (Hpcal4) was higher in the paired group. These genes encode proteins that regulate neuronal axonal morphology (Lsamp, Kif2), presynaptic vesicle cycling and release (Hpcal4 and NSF), and AMPA receptor maintenance in synapses (NSF). Quantitative real-time PCR (qPCR) revealed that Kif2 and Lsamp are expressed hours following fear conditioning but minutes after unpaired training. Hpcal4 is induced by paired stimulation only 5 hours after training. These results show that fear conditioning induces a unique temporal activation of molecular pathways involved in regulating synaptic transmission and axonal morphology in LA, which is different from non-associative stimulation.