Impaired single cell firing and long‐term potentiation parallels memory impairment following recurrent seizures
Impaired single cell firing and long‐term potentiation parallels memory impairment following recurrent seizures
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DOI：
10.1111/j.1460-9568.2007.05598.x
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发表时间：
2007-06
影响因子：
3.4
通讯作者：
Jun-Li Zhou;Tatiana N. Shatskikh;Xianzeng Liu;G. Holmes
中科院分区：
文献类型：
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作者：
Jun-Li Zhou;Tatiana N. Shatskikh;Xianzeng Liu;G. Holmes
癫痫患者存在记忆障碍的巨大风险。动物研究证实了这些临床观察结果，表明癫痫发作的啮齿动物的空间记忆功能受损。然而，癫痫发作诱导海马损伤的机制尚不清楚。在这里，我们研究了反复发作对水迷宫表现的影响，水迷宫表现是学习和记忆的行为指标，长时程增强（LTP;被认为是突触可塑性和记忆的测试）和位置细胞放电模式，空间记忆的单细胞指标。在10次氟乙酸诱导癫痫发作之前和之后，在自由活动大鼠的单独组中检查LTP和CA 1位置细胞活性。在第三组大鼠中检查水迷宫性能，其中五只先前诱导癫痫发作，五只对照。复发性氟乙酰癫痫发作与LTP的显著损害和峰值θ功率频率的降低相关。与基线记录相比，复发性癫痫发作后的位置细胞放电模式明显不精确，放电率较低且不稳定。早在两次癫痫发作后就观察到位置细胞放电受损，并在最后一次癫痫发作后持续至少72小时。在反复发作的动物中，水迷宫表现也显著受损。在海马体或其他几个易受癫痫发作影响的皮质区域，没有观察到细胞丢失或突触重组。这些结果表明，相对短暂的兴奋性事件，不产生可见的细胞损伤，但仍可能导致海马生理学的长期变化，可观察到位置细胞功能，LTP和空间记忆的损伤。
Patients with epilepsy are at substantial risk for memory impairment. Animal studies have paralleled these clinical observations, demonstrating impaired hippocampal function as measured by spatial memory in rodents subjected to seizures. However, the mechanism of seizure‐induced hippocampal impairment is unclear. Here we investigated the effects of recurrent seizures on water‐maze performance, a behavioural measure of learning and memory, long‐term potentiation (LTP; considered a test of synaptic plasticity and memory) and place‐cell firing patterns, a single‐cell indicator of spatial memory. LTP and CA1 place‐cell activity were examined in separate groups of freely moving rats, before and after 10 flurothyl‐induced seizures. Water maze performance was examined in a third group of rats, five with previously induced seizures and five controls. Recurrent flurothyl seizures were associated with marked impairment in LTP and a reduction in the frequency of the peak theta power. Compared to baseline recordings, place‐cell firing patterns following recurrent seizures were significantly less precise, had lower firing rates and were less stable. Impaired place‐cell firing was seen as early as after two seizures and persisted at least 72 h after the last seizure. Water‐maze performance was also significantly impaired in animals that underwent recurrent seizures. No cell loss or synaptic reorganization was observed in the hippocampus or in several other cortical areas that are vulnerable to seizures. These results demonstrate that relatively brief excitatory events, not producing visible cell damage, can nevertheless cause long‐lasting changes in hippocampal physiology, observable as impairments in place‐cell function, LTP and spatial memory.