匹罗卡品癫痫模型恐惧记忆减退的电生理学变化

Alteration of electrophysiology in pilocarpine mice model of epilepsy with impairment of contextual fear memory

目的探讨匹罗卡品诱导的癫痫小鼠模型恐惧记忆减退的机制以及电生理学的变化。方法建立腹腔注射微量匹罗卡品(PILO)诱发的颞叶癫痫小鼠模型,对致痫后24 h、2周和6周的小鼠海马切片CA1区域的神经元分别进行α-氨基-3-羧基-5-甲基异戊唑-4-丙酸(AMPA)受体介导的基础突触传递效率及长时程增强(LTP)形成的检测;以腹腔注射生理盐水的小鼠为对照组。结果与对照组相比,PILO诱发的癫痫早期(24 h)海马CA1神经元上AMPA受体介导的基础突触传递效率明显增高,LTP呈现增强的趋势(P>0.05);后期(6周)AMPA受体介导的基础突触传递效率与对照组已无明显差别,但LTP的形成被抑制(P<0.05)。结论LTP的抑制是场景恐惧记忆减退的发生机制。

Objective To explore the mechanism of impairment of the contextual fear memory in pilocarpine mice model of epilepsy, and detect the alteration of electrophysiology. Methods The temporal lobe epilepsy mouse model was established by peritoneal injection of pilocarpine. The α-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid receptor （AMPAR）-mediated basal synaptic transmission and the induction of long-term potentiation （LTP） on hippocampal CA1 were tested at 24 hours, 2 weeks and 6 weeks after model establishment. Mice with peritoneal injection of normal saline were served as controls. Results Compared with the controls, the AMPAR-mediated basal synaptic transmission on hippocampal CA1 was significantly increased in those at the early period （24 hours） of epilepsy induced by pilocarpine, and LTP displayed an increasing tendency（P 〉 0.05）. However, there was no significant difference in the AMPAR-mediated basal synaptic transmission on hippocampal CA1 between those at the later period （6 weeks） of epilepsy induced by pilocarpine and controls, while LTP was inhibited （ P 〈 0.05）. Conclusion The inhibition of LTP is involved in the mechanism of impairment of contextual fear memory.