Behavioral analysis of NR2C knockout mouse reveals deficit in acquisition of conditioned fear and working memory.
Behavioral analysis of NR2C knockout mouse reveals deficit in acquisition of conditioned fear and working memory.
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DOI：
10.1016/j.nlm.2011.01.008
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发表时间：
2011-05
影响因子：
2.7
通讯作者：
Dravid, Shashank M.
中科院分区：
文献类型：
--
作者：
Hillman, Brandon G.;Gupta, Subhash C.;Stairs, Dustin J.;Buonanno, Andres;Dravid, Shashank M.
N-甲基-D-天冬氨酸 (NMDA) 受体在兴奋性神经传递中发挥重要作用，并介导与学习和记忆相关的突触可塑性。 NMDA 受体由两个 NR1 和两个 NR2 亚基组成，NR2 亚基的特性赋予受体独特的电生理和药理学特性。含 NR2C 的受体在体内的确切作用尚不清楚。我们对 NR2C 敲除/nβ-半乳糖苷酶敲入小鼠进行了一系列行为测试，发现与野生型小鼠相比，自发活动、基础焦虑、强迫游泳不动、新物体识别、疼痛敏感性和参考记忆没有差异。然而，与野生型小鼠相比，NR2C 敲除小鼠在恐惧习得和工作记忆方面表现出缺陷。恐惧习得的缺陷与丘脑-杏仁核突触缺乏恐惧条件诱导的可塑性相关。这些发现表明，含有 NR2C 的受体在联想和执行学习中具有独特的作用，代表了认知缺陷和精神障碍（如创伤后应激障碍）的新治疗靶点。
N -methyl-D-aspartate (NMDA) receptors play an important role in excitatory neurotransmission and mediate synaptic plasticity associated with learning and memory. NMDA receptors are composed of two NR1 and two NR2 subunits and the identity of the NR2 subunit confers unique electrophysiologic and pharmacologic properties to the receptor. The precise role of NR2C-containing receptors in vivo is poorly understood. We have performed a battery of behavioral tests on NR2C knockout/nβ-galactosidase knock-in mice and found no difference in spontaneous activity, basal anxiety, forced-swim immobility, novel object recognition, pain sensitivity and reference memory in comparison to wildtype counterparts. However, NR2C knockout mice were found to exhibit deficits in fear acquisition and working memory compared to wildtype mice. Deficit in fear acquisition correlated with lack of fear conditioning-induced plasticity at the thalamo-amygdala synapse. These findings suggest a unique role of NR2C-containing receptors in associative and executive learning representing a novel therapeutic target for cognitive deficits and mental disorders such as post-traumatic stress disorder.
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影响因子：
7.6
作者：
Honey, RAE;Turner, DC;Honey, GD;Sharar, SR;Kumaran, D;Pomarol-Clotet, E;McKenna, P;Sahakian, B;Robbins, TW;Fletcher, P
通讯作者：
Fletcher, P
影响因子：
5.3
作者：
Cathala, L;Misra, C;Cull-Candy, S
通讯作者：
Cull-Candy, S
影响因子：
3.4
作者：
Castner, SA;Goldman-Rakic, PS;Williams, GV
通讯作者：
Williams, GV
影响因子：
5.3
作者：
Clarke, Richard J.;Johnson, Jon W.
通讯作者：
Johnson, Jon W.
影响因子：
5.3
作者：
Floresco, SB;Braaksma, DN;Phillips, AG
通讯作者：
Phillips, AG