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训练后内侧基底杏仁核复合体单次注射克仑特罗增强条件性位置偏爱记忆,并增加背侧海马突触部分的 ARC 蛋白表达。

Post-training intra-basolateral complex of the amygdala infusions of clenbuterol enhance memory for conditioned place preference and increase ARC protein expression in dorsal hippocampal synaptic fractions.

机构信息

School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX 75080, United States.

出版信息

Neurobiol Learn Mem. 2021 Nov;185:107539. doi: 10.1016/j.nlm.2021.107539. Epub 2021 Oct 12.

Abstract

The basolateral complex of the amygdala (BLA) is critically involved in modulation of memory by stress hormones. Noradrenergic activation of the BLA enhances memory consolidation and plays a necessary role in the enhancing or impairing effects of stress hormones on memory. The BLA is not only involved in the consolidation of aversive memories but can regulate appetitive memory formation as well. Extensive evidence suggests that the BLA is a modulatory structure that influences consolidation of arousing memories through modulation of plasticity and expression of plasticity-related genes, such as the activity regulated cytoskeletal-associated (Arc/Arg 3.1) protein, in efferent brain regions. ARC is an immediate early gene whose mRNA is localized to the dendrites and is necessary for hippocampus-dependent long-term potentiation and long-term memory formation. Post-training intra-BLA infusions of the β-adrenoceptor agonist, clenbuterol, enhances memory for an aversive task and increases dorsal hippocampus ARC protein expression following training on that task. To examine whether this function of BLA noradrenergic signaling extends to the consolidation of appetitive memories, the present studies test the effect of post-training intra-BLA infusions of clenbuterol on memory for the appetitive conditioned place preference (CPP) task and for effects on ARC protein expression in hippocampal synapses. Additionally, the necessity of increased hippocampal ARC protein expression was also examined for long-term memory formation of the CPP task. Immediate post-training intra-BLA infusions of clenbuterol (4 ng/0.2 µL) significantly enhanced memory for the CPP task. This same memory enhancing treatment significantly increased ARC protein expression in dorsal, but not ventral, hippocampal synaptic fractions. Furthermore, immediate post-training intra-dorsal hippocampal infusions of Arc antisense oligodeoxynucleotides (ODNs), which reduce ARC protein expression, prevented long-term memory formation for the CPP task. These results suggest that noradrenergic activity in the BLA influences long-term memory for aversive and appetitive events in a similar manner and the role of the BLA is conserved across classes of memory. It also suggests that the influence of the BLA on hippocampal ARC protein expression and the role of hippocampal ARC protein expression are conserved across classes of emotionally arousing memories.

摘要

杏仁核基底外侧复合体(BLA)在应激激素对记忆的调节中起着关键作用。去甲肾上腺素能激活 BLA 增强记忆巩固,并在应激激素对记忆的增强或损害效应中发挥必要作用。BLA 不仅参与厌恶记忆的巩固,而且还可以调节食欲记忆的形成。大量证据表明,BLA 是一种调节结构,通过调节可塑性和表达可塑性相关基因,如活性调节细胞骨架相关(Arc/Arg3.1)蛋白,来影响唤醒记忆的巩固,从而影响传出脑区的记忆巩固。ARC 是一种即刻早期基因,其 mRNA 定位于树突中,是海马依赖性长时程增强和长时记忆形成所必需的。训练后,BLA 内注射β-肾上腺素能激动剂克伦特罗可增强对厌恶任务的记忆,并增加训练后背侧海马 ARC 蛋白表达。为了研究 BLA 去甲肾上腺素能信号的这一功能是否扩展到食欲记忆的巩固,本研究测试了训练后 BLA 内注射克伦特罗对食欲条件性位置偏爱(CPP)任务的记忆的影响,以及对海马突触中 ARC 蛋白表达的影响。此外,还检查了增加海马 ARC 蛋白表达对 CPP 任务的长期记忆形成的必要性。训练后立即在 BLA 内注射克伦特罗(4ng/0.2µL)可显著增强对 CPP 任务的记忆。这种同样的记忆增强处理显著增加了背侧海马突触分数中,但不是腹侧海马突触分数中的 ARC 蛋白表达。此外,训练后立即在背侧海马内注射 Arc 反义寡核苷酸(ODN),减少 ARC 蛋白表达,可防止 CPP 任务的长期记忆形成。这些结果表明,BLA 中的去甲肾上腺素能活性以类似的方式影响对厌恶和食欲事件的长期记忆,BLA 的作用在记忆类别中是保守的。这也表明,BLA 对海马 ARC 蛋白表达的影响以及海马 ARC 蛋白表达的作用在情绪唤醒记忆的类别中是保守的。

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