Different temporal windows for contextual fear memory destabilisation in the amygdala and hippocampus

Different temporal windows for contextual fear memory destabilisation in the amygdala and hippocampus
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杏仁核和海马体情境恐惧记忆不稳定的不同时间窗口

DOI:
10.1101/434407
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发表时间:
2018
期刊:
--
影响因子:
--
通讯作者:
Lee J
Lee J
中科院分区:
--
文献类型:
--
作者:
Lee J

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再巩固是一个过程,在这个过程中,再次接触提醒会导致先前获得的记忆经历一个不稳定的过程,然后再稳定下来。杏仁核和海马区的不同分子机制被认为是不稳定的,包括CB1受体激活、蛋白质降解和AMPA受体交换;然而,大多数杏仁核研究使用了重新暴露前的干预措施,而那些在海马区的研究是在再次暴露后进行的。为了测试两种结构的不稳定时间窗口是否相似,我们在情景恐惧条件反射任务中训练了Lister蒙面大鼠,并在1天后进行记忆重新暴露,然后注射NMDA拮抗剂MK-801(0.1 mg/kg)或生理盐水,以阻止再巩固。同时,我们还进行了CB1拮抗剂SR141716A或其载体在海马区或杏仁核的局部注射,要么是在重新激活之前,要么是在重新激活之后。在海马区注入SR141716A可以阻止MK-801在再次暴露后的再巩固-阻断效应,但不能在再次暴露之前阻止。同时,在杏仁核,再次暴露前注入SR141716A会削弱MK-801对再巩固的阻断,尽管这种效应的时间依赖性不如在海马区那么明显。我们的结果表明,在再巩固过程中,CB1受体介导的记忆不稳定的时间窗口因大脑结构而异。这是否反映了这些结构参与的不同时间窗口,或者CB1受体在跨结构的不稳定中所扮演的不同角色,仍是未来研究的一个悬而未决的问题。
Reconsolidation is a process in which re-exposure to a reminder causes a previously acquired memory to undergo a process of destabilisation followed by subsequent restabilisation. Different molecular mechanisms have been postulated for destabilisation in the amygdala and hippocampus, including CB1 receptor activation, protein degradation and AMPA receptor exchange; however, most of the amygdala studies have used pre-re-exposure interventions, while those in the hippocampus have performed them after re-exposure. To test whether the temporal window for destabilisation is similar across both structures, we trained Lister Hooded rats in a contextual fear conditioning task, and 1 day later performed memory re-exposure followed by injection of either the NMDA antagonist MK-801 (0.1 mg/kg) or saline in order to block reconsolidation. In parallel, we also performed local injections of either the CB1 antagonist SR141716A or its vehicle in the hippocampus or in the amygdala, either immediately before or immediately after reactivation. Infusion of SR141716A in the hippocampus prevented the reconsolidation-blocking effect of MK-801 when performed after re-exposure, but not before it. In the amygdala, meanwhile, pre-reexposure infusions of SR141716A impaired reconsolidation blockade by MK-801, although the time-dependency of this effect was not as clear as in the hippocampus. Our results suggest the temporal windows for CB1-receptor-mediated memory destabilisation during reconsolidation vary between brain structures. Whether this reflects different time windows for engagement of these structures or different roles played by CB1 receptors in destabilisation across structures remains an open question for future studies.
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