Role of hippocampal NMDA receptors in trace eyeblink conditioning

Role of hippocampal NMDA receptors in trace eyeblink conditioning
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DOI:
10.1016/j.brainres.2005.01.068
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发表时间:
2005-03-28
期刊:
影响因子:
2.9
通讯作者:
Mishina, M
Mishina, M
中科院分区:
医学3区
文献类型:
--
作者:
Sakamoto, T;Takatsuki, K;Mishina, M

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我们观察了急性背侧海马区注射竞争性N-甲基-D-天冬氨酸(NMDA)受体拮抗剂2-氨基-5-膦-戊酸(APV)对C57BL/6小鼠背景恐惧条件反射和经典眨眼条件反射的影响。当训练前10-40分钟注射APV时,APV严重损害情境恐惧条件反射。因此,在此条件下注射APV足以抑制海马NMDA受体。为了探讨海马神经元NMDA受体在瞬目条件反射中的作用,我们在注射APV后10-40分钟内对小鼠进行每日训练。在延迟眨眼条件反射中,非条件刺激(US)延迟并与条件刺激(CS)同时终止,注射APV的小鼠获得条件性反应(CRS),而注射人工脑脊液(ACSF)的对照组小鼠获得条件反应(CRS)。然而,在示踪眨眼条件下,CS和US以500ms的无刺激示踪间隔分开,注射APV的小鼠在获得CR方面表现出严重的障碍。APV和ACSF注射小鼠的假条件反射无显著差异。这些结果提供了证据,证明背侧海马区的NMDA受体在长痕迹眨眼条件反射的获得中起关键作用。(C)2005 Elsevier B.V.保留所有权利。
We examined the effects of acute injections of competitive N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV) into the dorsal hippocampus on contextual fear conditioning and classical eyeblink conditioning in C57BL/6 mice. When injected 10 to 40 min before training, APV severely impaired contextual fear conditioning. Thus, APV injection under these conditions was sufficient to suppress hippocampal NMDA receptors. To investigate the role of hippocampal NMDA receptors on eyeblink conditioning, we carried out daily training of mice during 10-40 min after injection of APV. In the delay eyeblink conditioning, in which the unconditioned stimulus (US) is delayed and terminates simultaneously with the conditioned stimulus (CS), APV-injected mice acquired the conditioned responses (CRs) as well as artificial cerebrospinal fluid (aCSF)-injected control mice did. However, in the trace eyeblink conditioning, in which the CS and US were separated by a stimulus-free trace interval of 500 ms, APV-injected mice showed severe impairment in acquisition of the CR. There was no significant difference in pseudo-conditioning between APV- and aCSF-injected mice. These results provide evidence that the NMDA receptor in the dorsal hippocampus is critically involved in acquisition of the CR in long trace eyeblink conditioning. (c) 2005 Elsevier B.V. All rights reserved.