CNQX对清醒大鼠习得性LTP中海马DG区谷氨酸浓度的影响  

Effect of CNQX on Extracellular Levels of Glutamate in the Hippocampal Dentate Gyrus During Learning-dependent LTP in Free-moving Conscious Rats

作　　者：孙志刚[1] 姜岩[1] 包金锁[1] 金秀吉[2] 金元哲[2] 金清华[2] 

机构地区：[1]内蒙古民族大学附属医院神经外科研究所,内蒙古通辽028000 [2]延边大学基础医学院生理学与病理生理学教研部,吉林延吉133000

出　　处：《内蒙古医学杂志》2008年第8期897-902,共6页Inner Mongolia Medical Journal

基　　金：国家自然科学基金资助项目(No.30760064和No.30460041)

摘　　要：目的:观察条件反射的建立和消退过程中,ɑ-氨基羟甲基恶唑丙酸(AMPA)受体拮抗剂对自由活动大鼠海马齿状回(DG)细胞外液中Glu浓度的影响,并进一步探讨它们与习得性突触效应长时程增强(LD-LTP)和行为学习之间的关系。方法:本实验使用脑部微量透析法、脑部微量注射法、高效液相色谱法、慢性埋植电极技术以及行为学习监测与电生理记录相结合的实验方法。结果:未进行条件反射训练大鼠海马DG注射CNQX后,并不影响DG区细胞外液中的Glu水平,但其PS幅值从注射前的100%明显下降到65.47%±13.82%(P<0.01)。在条件反射的训练过程中,DG区注射Ringer’s液,Glu浓度出现明显增加,而随着条件反射消退,又逐渐回降,这与DG区群体峰电位峰值以及行为正确反应率的变化呈平行关系;DG区微量注射CNQX,明显抑制条件反射的形成,而且随着训练天数的增加,Glu浓度逐渐增加达到训练开始前的285.51%±43.83%(P<0.01),但PS幅值却没有明显的变化(P>0.05)。结论:AMPA受体在海马DG区习得性LTP的形成过程中起触发作用,此受体的激活是海马DG区习得性LTP形成的必要条件。Objective：To investigate the neurochemical mechanisms responsible for learning dependent long -term potentiation（LTP）, the effect of CNQX on extracellular levels of glutamate（Glu）was measured in hippocampal dentate gyrus（DG）region during the period of establishment and extinction of the conditioned reflex in free - moving conscious rats. Methods. The concentrations of amino acids including Glu was measured by microdialysis and high - performance liquid chromatography （HPLC） methods and CNQX （60nmol/L） was adminisu ated by local- microinjection. The population spike （PS）, a parameter of LTP, and conditional reflex were exa mined by implanted electrodes and combining electrophysiological-behavioral methods. Results：①There is no significant changes in the extracellular levels of Glu when local- microinjection of CNQX（60μmol/L）into the DG region without training P i〉 0.05）, but PS amplitude is significantly reduced（ P 〈 0.01 ）. ②In the control group, the extracellular levels of Glu in the DG region are significantly increased（P 〈 0. 001） during the establishment of conditioned reflex and gradually returned following the extinction of conditioned reflex. The changes of Glu are correlated to the change of PS and both changes roughly follow the correct rate of behavior. ③Although the changes of PS are significantly attenuated, the concentrations of Glu are still significantly increased（P 〈 0.05）by local-microinjection of CNQX. The establishment of conditioned reflex is significantly prevented by CNQX. Conclusion： AMPA receptor shows the trigger action in the hippocampal learning- dependent LTP.

关 键 词：海马齿状回 GLU 习得性LTP 学习记忆 CNQX 

分 类 号：Q427[生物学—神经生物学] R338.2[生物学—生理学]