Institute of Neurosciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, People's Republic of China.
Epilepsy Behav. 2010 Apr;17(4):448-54. doi: 10.1016/j.yebeh.2010.02.008. Epub 2010 Mar 23.
To explore the mechanism underlying the development of learning deficits in patients with epilepsy, we generated a mouse model for temporal lobe epilepsy by intraperitoneally injecting mice with pilocarpine with lithium chloride, and investigated time-dependent changes in both contextual fear memory of those model mice and long-term potentiation (LTP) in hippocampal CA1 neurons 1 day, 2 weeks, and 6 weeks after the onset of status epilepticus (SE). Fear memory formation did not change 1 day and 2 weeks after the onset of SE, but was significantly reduced after 6 weeks. Induction of LTP was enhanced 1 day after the onset of SE, but returned to the normal level 2 weeks later, and was almost completely attenuated after 6 weeks. The enhancement of LTP was accompanied by an increase in output responses of excitatory postsynaptic potentials, whereas suppression of LTP was accompanied by alteration of the ratio of paired pulse facilitation. These results indicate that time-dependent changes of LTP induction have a causal role in the development of learning deficits of epilepsy patients.
为了探究癫痫患者学习能力下降的潜在机制，我们通过腹腔注射匹罗卡品和氯化锂的方法构建了颞叶癫痫的小鼠模型，并在癫痫持续状态（SE）发作后 1 天、2 周和 6 周，研究了模型小鼠的情景恐惧记忆和海马 CA1 神经元长时程增强（LTP）的时间依赖性变化。SE 发作后 1 天和 2 周，恐惧记忆形成没有改变，但在 6 周后显著降低。LTP 的诱导在 SE 发作后 1 天增强，但 2 周后恢复正常水平，6 周后几乎完全减弱。LTP 的增强伴随着兴奋性突触后电位输出反应的增加，而 LTP 的抑制伴随着成对脉冲易化比值的改变。这些结果表明，LTP 诱导的时间依赖性变化在癫痫患者学习能力下降的发展中起着因果作用。
