Institute for Physiology I, Muenster, Germany.
Epilepsia. 2011 Feb;52(2):337-46. doi: 10.1111/j.1528-1167.2010.02758.x. Epub 2010 Nov 3.
The relationship between epilepsy and fear has received much attention. However, seizure-modulated fear and physiologic or structural correlates have not been examined systematically, and the underlying basics of network levels remain unclear to date. Therefore, this project was set up to characterize the neurophysiologic basis of seizure-related fear and the contribution of the amygdala-hippocampus system.
The experimental strategy was composed of the following steps: (1) use of the mouse pilocarpine model of temporal lobe epilepsy (TLE); (2) behavioral analyses of anxiety states in the elevated plus maze test, light-dark avoidance test, and Pavlovian fear conditioning; and (3) probing neurophysiologic activity patterns in amygdala-hippocampal circuits in freely behaving mice.
Our results displayed no significant differences in basic anxiety levels comparing mice that developed spontaneous recurrent seizures (SRS) and controls. Furthermore, conditioned fear memory retrieval was not influenced in SRS mice. However, during fear memory extinction, SRS mice showed an extended freezing behavior and a maintained amygdala-hippocampal theta frequency synchronization compared to controls.
These results indicate specific alterations in conditioned fear behavior and related neurophysiologic activities in the amygdala-hippocampal network contributing to impaired fear memory extinction in mice with TLE. Clinically, the nonextinguished fear memories may well contribute to the experience of fear in patients with TLE.
癫痫与恐惧之间的关系受到了广泛关注。然而，目前尚未系统地研究发作调节的恐惧以及生理或结构相关性，并且网络水平的潜在基础迄今仍不清楚。因此，本项目旨在描述与癫痫相关的恐惧的神经生理基础以及杏仁核-海马系统的贡献。
实验策略包括以下步骤：（1）使用颞叶癫痫（TLE）的小鼠匹鲁卡品模型；（2）在高架十字迷宫测试、明暗回避测试和条件性恐惧训练中分析焦虑状态；（3）在自由活动的小鼠中探测杏仁核-海马回路中的神经生理活动模式。
我们的结果显示，自发复发性癫痫（SRS）小鼠与对照组相比，基本焦虑水平没有显著差异。此外，SRS 小鼠的条件性恐惧记忆检索不受影响。然而，在恐惧记忆消退期间，SRS 小鼠与对照组相比，表现出更长时间的冻结行为和维持的杏仁核-海马θ频率同步。
这些结果表明，在 TLE 小鼠的杏仁核-海马网络中，条件性恐惧行为和相关神经生理活动存在特定改变，导致恐惧记忆消退受损。临床上，未消退的恐惧记忆可能是 TLE 患者感到恐惧的原因之一。
