NMDA受体在海马CA_3区习得性LTP保持中的作用

ROLE OF N-METHYL-D-ASPARTATE RECEPTOR IN THE MAINTENANCE OF LEARNING-DEPENDENT LONG-TERM POTENTIATION ON RAT HIPPOCAMPAL CA_3 AREA

在大鼠明暗分辨学习的建立和巩固过程中,通过与记录电极一起慢性埋植于海马CA_3区的注药管微量注射NMDA受体的特异性拮抗剂2-amino-5-phosphonovaleric acid(APV),观察对海马CA_3区突触效应及与之相关的习得性行为的影响。结果如下:(1)在动物经训练PS峰幅值刚增大至最高水平后,即在习得性LTP刚好形成后,每实验单元先于CA_3区注射AFV 1μl(2mmol/L),然后在药物有效作用时间内再进行训练,则PS峰值不能随训练而保持在最高水平,相反经8个实验单元,PS峰值降至实验前水平;相应地动物的正确反应率不能随训练而巩固,反而下降至10％以下。(2)在动物习得性LTP已形成并经一单元训练PS保持在最高水平后,于每实验单元训练前注射APV 1μl(2mmol/L),PS峰值同样不会随训练而保持在最高水平,经14个实验单元注药和训练,PS峰值逐渐降至实验前水平,相应地动物行为的正确反应率也降至10％以下,习得性行为消退,不过其消退速度比前一情况的动物为慢,说明习得性LTP发展情况不同,APV的作用效率有差别。结果表明:NMDA受体在习得性LTP的巩固中起着重要作用。

The effect of microinjection of 2-amino-5-phosphonovaleric acid (APV),a selective NMDA receptor antagonist, into the rat hippocampal CA_3 area on thesynaptic efficacy and related conditioned behavior during the acquisition andconsolidation of discrimination learning behavior was examined. The results showed: (1) After population spike (PS) amplitude had just increas-ed to the maximum through training i.e. learning-dependent LTP had just fromed,APV 1 μl (2 mmol/L) was injected into CA_3 area, then the rats were trained dur-ing the time of efficacy of the drug in every experimental block. The result dem-onstrated that the PS amplitude could not be maintained at the highest level butdecreased to the pre-experiment level after 8 blocks. Correct response percentageof rats could not be consolidated with further training but decreased to less than 10%.(2) After the PS amplitude had kept up at the highest level, APV 1 μl (2 mmol/L)was injected into CA_3 area, then the rats were trained during the time of efficacy ofthe drug in every experimental block, in which case the PS amplitude also couldnot be maintained at the highest level but decreased to the pre-experiment levelafter 14 blocks. Correlatively, when the correct response percentage of rats de-creased gradually to less than 10%, the conditioned response of the animals extin-guished, but its extinction speed was slower than it was in result (1). These results suggest that the NMDA receptor in CA_3 area plays an impor-tant role in the maintenance of the learning-dependent long-term potentiation.