N-methyl-D-aspartate receptors play important roles in acquisition and expression of the eyeblink conditioned response in glutamate receptor subunit δ2 mutant mice
N-methyl-D-aspartate receptors play important roles in acquisition and expression of the eyeblink conditioned response in glutamate receptor subunit δ2 mutant mice
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DOI：
10.1016/j.neuroscience.2005.07.026
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Kirino, Y
中科院分区：
文献类型：
--
作者：
Kato, Y;Takatsuki, K;Kirino, Y
众所周知，经典的眨眼条件作用在很大程度上取决于小脑。显然与此一致的是，谷氨酸受体亚单位82缺失突变小鼠在小脑皮质存在严重的形态和功能缺陷，在延迟范式中严重受损。然而，这些突变小鼠成功地在跟踪范式中学习，甚至在“0-痕迹范式”中也是如此，在这种范式中，无条件刺激在条件刺激终止后立即开始。我们先前的研究表明，与野生型小鼠不同，在谷氨酸受体亚单位82缺失的小鼠中，海马体和M胆碱受体在‘0-TRACE范式中起着关键作用，这表明前脑对这类突变小鼠的0-TRACE条件作用有很大贡献。在本研究中，我们研究了N-甲基-D-天冬氨酸受体在谷氨酸受体亚单位82缺失突变小鼠0踪迹眨眼条件反射中的作用。小鼠腹腔注射非竞争性N-甲基-D-天冬氨酸受体拮抗剂(+)MK-801(0.1 mg/kg)或生理盐水，条件刺激为350ms纯音条件刺激，然后是100ms眼眶周围休克非条件刺激。与注射生理盐水的谷氨酸受体亚基82缺失突变小鼠相比，注射(+)MK-801的谷氨酸受体亚基82缺失突变小鼠在条件性反应的获得方面表现出严重的损害。而野生型小鼠注射(+)MK-801对0踪迹条件性反应的获得无影响。在将注射液由(+)MK-801改为生理盐水后，谷氨酸受体亚单位82缺失突变小鼠的条件性反应表现出快速和部分的恢复。另一方面，当注射溶液从生理盐水改为(+)MK-801时，谷氨酸受体亚单位82缺失突变小鼠的前获得性条件性反应的表达明显受损，而野生型小鼠的表达受损较小。注射(+)MK-801对谷氨酸受体亚基82缺失突变小鼠和野生型小鼠的自发眨眼频率和惊厥眨眼频率均无明显影响。这些结果表明，N-甲基-D-天冬氨酸受体在谷氨酸受体亚单位82缺失突变小鼠的条件反应的获得和表达中起关键作用。(C)2005年由爱思唯尔有限公司代表IBRO出版。
Classical eyeblink conditioning has been known to depend critically on the cerebellum. Apparently consistent with this, glutamate receptor subunit 82 null mutant mice, which have serious morphological and functional deficiencies in the cerebellar cortex, are severely impaired in delay paradigm. However, these mutant mice successfully learn in trace paradigm, even in '0-trace paradigm,' in which the unconditioned stimulus starts just after the conditioned stimulus terminates. Our previous studies revealed that the hippocampus and the muscarinic acetylcholine receptors play crucial roles in '0-trace paradigm in glutamate receptor subunit 82 null mutant mice unlike in wild-type mice, suggesting a large contribution of the forebrain to 0-trace conditioning in this type of mutant mice. In the present study, we investigated the role of N-methyl-D-aspartate receptors in 0-trace eyeblink conditioning in glutamate receptor subunit 82 null mutant mice. Mice were injected intraperitoneally with the noncompetitive N-methyl-D-aspartate receptor antagonist (+)MK-801 (0.1 mg/kg) or saline, and conditioned with 350-ms tone conditioned stimulus followed by 100-ms periorbital shock unconditioned stimulus. Glutamate receptor subunit 82 null mutant mice that received (+)MK-801 injection exhibited a severe impairment in acquisition of the conditioned response, compared with the saline-injected glutamate receptor subunit 82 null mutant mice. In contrast, wild-type mice were not impaired in acquisition of 0-trace conditioned response by (+)MK-801 injection. After the injection solution was changed from (+)MK-801 to saline, glutamate receptor subunit 82 null mutant mice showed a rapid and partial recovery of performance of the conditioned response. On the other hand, when the injection solution was changed from saline to (+)MK-801, glutamate receptor subunit 82 null mutant mice showed a marked impairment in expression of the pre-acquired conditioned response, whereas impairment of the expression was small in wild-type mice. Injection of (+)MK-801 had no significant effects on spontaneous eyeblink frequency or startle eyeblink frequency to the tone conditioned stimulus in either glutamate receptor subunit 82 null mutant mice or wild-type mice. These results suggest that N-methyl-D-aspartate receptors play critical roles both in acquisition and expression of the conditioned response in 0-trace eyeblink conditioning in glutamate receptor subunit 82 null mutant mice. (c) 2005 Published by Elsevier Ltd on behalf of IBRO.