AMYGDALA KINDLING DISRUPTS TRACE AND DELAY FEAR CONDITIONING WITH PARALLEL CHANGES IN FOS PROTEIN EXPRESSION THROUGHOUT THE LIMBIC BRAIN

AMYGDALA KINDLING DISRUPTS TRACE AND DELAY FEAR CONDITIONING WITH PARALLEL CHANGES IN FOS PROTEIN EXPRESSION THROUGHOUT THE LIMBIC BRAIN
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DOI:
10.1016/j.neuroscience.2014.01.040
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发表时间:
2014-04-18
期刊:
影响因子:
3.3
通讯作者:
Kalynchuk, L. E.
Kalynchuk, L. E.
中科院分区:
医学3区
文献类型:
--
作者:
Botterill, J. J.;Fournier, N. M.;Kalynchuk, L. E.

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众所周知,杏仁核点燃会增加无条件的恐惧和焦虑。然而,对于这种形式的点燃是否会引起介导恐惧学习和恐惧记忆检索的神经回路功能变化,人们知之甚少。为了解决这个问题,我们研究了短期(即 30 次刺激)和长期(即 99 次刺激)杏仁核点燃对大鼠追踪和延迟恐惧条件反射的影响,这两种恐惧条件反射是主要依赖于海马体和杏仁核的厌恶性学习任务。记忆检索后,我们用 Fos(即早期基因 c-fos 的蛋白质产物)分析了神经活动模式。我们发现点燃对微量恐惧调节任务的获得没有影响,但它确实选择性地损害了这种恐惧记忆的检索。相比之下,在延迟恐惧调节任务中,点燃会破坏恐惧记忆的获取和检索。我们还发现,火种引起的记忆检索障碍伴随着海马体、海马旁体和杏仁核的几个亚区域中 Fos 表达的减少。有趣的是,微量条件反射任务中冻结的减少与海马和海马旁区域 Fos 表达的抑制显着相关,而延迟条件反射任务中冻结的减少与海马、海马旁和杏仁环路中 Fos 表达的抑制显着相关。总的来说,这些结果表明杏仁核点燃促进了涉及特定类型的恐惧学习和记忆的大脑区域的功能变化。 (C) 2014 年国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Amygdala kindling is well known to increase unconditioned fear and anxiety. However, relatively little is known about whether this form of kindling causes functional changes within the neural circuitry that mediates fear learning and the retrieval of fear memories. To address this issue, we examined the effect of short- (i.e., 30 stimulations) and long-term (i.e., 99 stimulations) amygdala kindling in rats on trace and delay fear conditioning, which are aversive learning tasks that rely predominantly on the hippocampus and amygdala, respectively. After memory retrieval, we analyzed the pattern of neural activity with Fos, the protein product of the immediate early gene c-fos. We found that kindling had no effect on acquisition of the trace fear conditioning task but it did selectively impair retrieval of this fear memory. In contrast, kindling disrupted both acquisition and retrieval of fear memory in the delay fear conditioning task. We also found that kindling-induced impairments in memory retrieval were accompanied by decreased Fos expression in several subregions of the hippocampus, parahippocampus, and amygdala. Interestingly, decreased freezing in the trace conditioning task was significantly correlated with dampened Fos expression in hippocampal and parahippocampal regions whereas decreased freezing in the delay conditioning task was significantly correlated with dampened Fos expression in hippocampal, parahippocampal, and amygdaloid circuits. Overall, these results suggest that amygdala kindling promotes functional changes in brain regions involved in specific types of fear learning and memory. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.