Hippocampal train stimulation modulates recall of fear extinction independently of prefrontal cortex synaptic plasticity and lesions
Hippocampal train stimulation modulates recall of fear extinction independently of prefrontal cortex synaptic plasticity and lesions
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DOI：
10.1101/lm.204806
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发表时间：
2006-05-01
影响因子：
2
通讯作者：
Garcia, Rene
中科院分区：
文献类型：
--
作者：
Farinelli, Missa;Deschaux, Olivier;Garcia, Rene
研究表明，恐惧消退后，长时程增强(LTP)发生在丘脑内侧背侧部(MD)和内侧前额叶皮质(MPFC)之间以及海马区(HPC)和mPFC之间，并与消退保持有关。然而，最近的损伤研究表明，MD和mPFC的联合损伤不会干扰消退学习和保持，而背侧HPC的失活会扰乱恐惧消退记忆。我们在大鼠身上发现，训练后即刻的HPC低频刺激(LFS)抑制了HPC-mPFC通路中与灭绝相关的LTP，并导致了灭绝回忆的困难。几个小时后应用HPC破伤风，未能重新建立mPFC LTP，但促进了对灭绝的回忆。训练后延迟的HPC US也引起了mPFC的去增强和灭绝回忆的困难。HPC破伤风消除了这两种影响。我们还发现，mPFC的损伤只在灭绝训练后接受HPC LFS的大鼠中诱导恐惧返回。HPC破伤风也逆转了HPC US对毁损大鼠的这一行为效应。这些数据表明，HPC在恐惧消退过程中与mPFC相互作用，但可以独立于这种相互作用调节恐惧消退。
It has been shown that long-term potentiation (LTP) develops in the connection between the mediodorsal thalamus (MD) and the medial prefrontal cortex (mPFC) and between the hippocampus (HPC) and the mPFC following fear extinction, and correlates with extinction retention. However, recent lesion studies have shown that combined lesions of the MD and mPFC do not interfere with extinction learning and retention, while inactivation of the dorsal HPC disrupts fear extinction memory. Here we found in rats that immediate post-training HPC low-frequency stimulation (LFS) suppressed extinction-related LTP in the HPC-mPFC pathway and induced difficulties in extinction recall. HPC tetanus, applied several hours later, failed to re-establish mPFC LTP but facilitated recall of extinction. Delayed post-training HPC US also provoked mPFC depotentiation and difficulties with extinction recall. HPC tetanus abolished these two effects. We also found that damage to the mPFC induced fear return only in rats that received HPC LFS following extinction training. HPC tetanus also reversed this behavioral effect of HPC US in lesioned rats. These data suggest that the HPC interacts with the mPFC during fear extinction, but can modulate fear extinction independently of this interaction.