热性癫痫发作大鼠海马齿状回外侧支的可塑性和再可塑性(英文)

Plasticity and metaplasticity of lateral perforant path in hippocampal dentate gyrus in a rat model of febrile seizure

热性癫痫发作是儿童常见病,能损害认知功能,而突触可塑性和再可塑性(metaplasticity)是维系大脑认知功能的重要神经基础。本文通过脑片灌流和细胞外场电位记录术研究了热性癫痫发作大鼠海马齿状回外侧支的突触可塑性和再可塑性。制作对照组和热性癫痫发作组大鼠的脑切片后,记录电极置于齿状回外侧支的外分子层获取兴奋性突触后电位。双极刺激电极根据不同需要分别安放于齿状回外侧支或门区。结果显示,大鼠海马齿状回外侧支给予100Hz的条件刺激后,对照组和热性癫痫发作大鼠海马齿状回外侧支长时程增强(long-term potentiation,LTP)的幅度均没有显著改变。而在齿状回外侧支给予10Hz的预先刺激,再施加相同的条件刺激后,对照组外侧支LTP幅度明显下降,条件刺激后1h的相对兴奋性突触后电位(field excitatory postsynaptic potentials,fEPSP)为1.10±0.26;而热性癫痫发作组则表现出明显的LTP,条件刺激后1h的相对fEPSP为1.35±0.2,与对照组比较有显著性增强(P<0.05)。在齿状回门区实施10Hz的预先逆行性刺激,再施加与前述实验相同的条件刺激后,对照组外侧支LTP幅度亦出现明显下降,条件刺激后1h的相对fEPSP为1.15±0.14;而热性癫痫发作组表现出明显的LTP,条件刺激后1h的相对fEPSP分别为1.47±0.19,与对照组比较有显著性增强(P<0.05)。以上结果表明,热性癫痫发作可以在不改变突触可塑性的情况下影响再可塑性,从而导致神经损伤,该现象提示热性癫痫发作能通过不同途径增加神经兴奋性。

Febrile seizure（FS） is common in childhood and can impair cognitive function.The potential to exhibit plasticity at many synapses appears to be modulated by prior synaptic activity.This intriguing higher-order form of plasticity has been termed metaplasticity.Plasticity and metaplasticity have been considered to be one of the most important neurological fundaments of learning and memory.In the present study,field potential recording was carried out to detect the effects of FS on plasticity and metaplasticity in the lateral perforant path of rat hippocampus.Brain slices from rat pups of FS model were prepared and superfused.The recording electrodes were placed within the outer molecular layer for recording of lateral perforant path field excitatory postsynaptic potentials（fEPSP）.Stimulation of the lateral perforant path and the dentate hilar region was carried out by placing bipolar stimulating electrodes within the outer molecular layer and hilus,respectively.The results showed that long term potentiation（LTP） of control and FS rats didn＇t show significant difference after 100 Hz conditioning stimulation.Subjected to 10 Hz priming stimulation applied to lateral perforant path or dentate hilar region 40 min prior to 100 Hz conditioning,the LTP of control group was inhibited,while the LTP of FS rats remained constant.Normalized fEPSP slope 1 h after tetanization of control group was 1.10±0.26 and 1.15±0.14 after homosynaptic and antidromic priming stimulation respectively.On the contrast,FS group didn＇t show any depression of LTP after homosynaptic and antidromic priming stimulation,normalized fEPSP slope 1 h after tetanization being 1.35±0.2 and 1.47±0.19,respectively.These results suggest that FS would impair lateral perforant path metaplasticity without affecting LTP.These findings represent an intriguing phenomenon of FS-caused brain damage and imply the injury of excitatory status in different pathways.