Novelty causes time-dependent retrograde amnesia for one-trial avoidance in rats through NMDA receptor- and CaMKII-dependent mechanisms in the hippocampus
Novelty causes time-dependent retrograde amnesia for one-trial avoidance in rats through NMDA receptor- and CaMKII-dependent mechanisms in the hippocampus
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DOI：
10.1046/j.1460-9568.1999.00742.x
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发表时间：
1999-09-01
影响因子：
3.4
通讯作者：
Medina, JH
中科院分区：
文献类型：
--
作者：
Izquierdo, I;Schröder, N;Medina, JH
在一次尝试抑制性回避训练后1h，暴露于新环境(开阔场地)2min，阻碍了对24 h后测量的回避任务的记忆。无论回避训练的足部电击强度有多大，都能看到这种效果。如果在回避训练之前5分钟或之后6小时暴露于新奇事物，或者如果动物没有将空旷的场地视为新的并做出相应的反应，则不会看到效果。回避训练后1h出现的新奇记忆效应可被海马区注射D-2-氨基-5-膦-戊酸或1-(N，O-bis-[5-isoquinolinylsulphonyl]-N-methyl-L-tyrosyl)-4-phenylpiperazine，KN62，每侧100mmol.)阻断，但不能被C32H25N3O6(KT5720，每侧90mM摩尔)所阻断。在开阔的田野上，通过第一分钟和第二分钟之间探索次数的减少来衡量，这是一种习惯化。AP5和KN62可削弱这种习惯性，但不影响KT5720。在暴露于回避任务5分钟后、之前1小时或6小时的小组中，对开阔场地的探索是相似的。因此，两种任务的效果之间不存在互惠关系：对于一次尝试回避任务来说，新颖性是健忘的，但相反的情况并非如此。新颖性的遗忘效应似乎依赖于N-甲基-D-天冬氨酸(NMDA)受体和钙/钙调蛋白依赖的蛋白激酶II(CaMKII)，而不是依赖于PKA的习惯性学习。
Exposure to a novel environment (an open field) for 2 min, 1 h after one-trial inhibitory avoidance training, hindered memory of the avoidance task measured 24 h later. The effect was seen regardless of the intensity of the avoidance training footshock. The effect was not seen if the exposure to novelty was carried out 5 min before, or 6 h after, the avoidance training, or if the animals did not perceive the open field as new and react accordingly. The amnesic effect of the novelty presented 1 h after avoidance training was blocked by the intrahippocampal infusion of D-2-amino-5-phosphono-pentanoic acid (AP5, 25 nmoles per side) or 1-(N,O-bis-[5-isoquinolinylsulphonyl]-N-methyl-L-tyrosyl)-4-phenylpiperazine (KN62, 100 mmoles per side) but not by that of C32H25N3O6 (KT5720, 90 mu moles per side) given 5 min before the novelty. In the open field there was habituation, measured by the decrease in exploration between the first and second minute. AP5 and KN62 impaired this habituation, but not KT5720. Exploration of the open field was similar in the groups exposed to the avoidance task 5 min later, or 1 h or 6 h before. Therefore, there was no reciprocity between the effect of the two tasks: novelty was amnesic for the one-trial avoidance task, but the opposite was not true. The amnesic effect of novelty appears to rely on N-methyl-D-aspartate (NMDA) receptor- and calcium/calmodulin-dependent protein kinase II (CaMKII)-dependent, but not on PKA-dependent, aspects of its habituation learning.