αCaMKII autophosphorylation controls exploratory activity to threatening novel stimuli
αCaMKII autophosphorylation controls exploratory activity to threatening novel stimuli
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DOI：
10.1016/j.neuropharm.2011.08.036
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发表时间：
2011-12-01
影响因子：
4.7
通讯作者：
Fernandes, Cathy
中科院分区：
文献类型：
--
作者：
Easton, Alanna C.;Lucchesi, Walter;Fernandes, Cathy
α CaMKII的自磷酸化被认为是Ca（2+）瞬变的“分子记忆”，是食欲不振的关键机制，但在食欲、动机性学习和记忆中则不那么重要。虽然有越来越多的研究表明α CaMKII通常参与对威胁或恐惧刺激的行为反应，但对自磷酸化的贡献知之甚少。本研究探讨了α CaMKII自磷酸化如何控制对新的、潜在的威胁性刺激的焦虑样行为反应。我们在一系列系统的行为测试中测试了纯合和杂合T286 A α CaMKII自磷酸化缺陷小鼠和野生型。纯合子突变体在旷场试验中更活跃，在光/暗试验中表现出减少的焦虑相关行为，但这些发现被hypermotorism表型混淆。高架十字迷宫的分析显示，α CaMKII自磷酸化缺陷小鼠的焦虑相关行为显著减少，这似乎介导了过度运动反应。一个分析的家庭笼的行为，既没有新颖的，也没有威胁性的刺激，表现出基因型之间的自发活动没有差异。在α CaMKII自磷酸化缺陷小鼠的新物体探索测试中没有观察到运动增加，这意味着对离散的新刺激不会发生活动过度。目前的数据表明，α CaMKII自磷酸化缺陷小鼠的行为不能简单地描述为低焦虑表型。相反，它表明，α CaMKII自磷酸化影响运动反应的新环境是潜在的，但不一定是威胁。(C)2011爱思唯尔有限公司保留所有权利。
Autophosphorylation of alpha CaMKII is regarded as a 'molecular memory' for Ca(2+) transients and a crucial mechanism in aversely, but less so in appetitively, motivated learning and memory. While there is a growing body of research implicating alpha CaMKII in general in behavioral responses to threat or fearful stimuli, little is known about the contribution of the autophosphorylation. The present study asked how alpha CaMKII autophosphorylation controls anxiety-like behavioral responses toward novel, potentially threatening stimuli. We tested homozygous and heterozygous T286A alpha CaMKII autophosphorylation deficient mice and wild types in a systematic series of behavioral tests. Homozygous mutants were more active in the open field test and showed reduced anxiety-related behavior in the light/dark test, but these findings were confounded by a hyperlocomotor phenotype. The analysis of elevated plus maze showed significantly reduced anxiety-related behavior in the alpha CaMKII autophosphorylation-deficient mice which appeared to mediate a hyperlocomotor response. An analysis of home cage behavior, where neither novel nor threatening stimuli were present, showed no differences in locomotor activity between genotypes. Increased locomotion was not observed in the novel object exploration test in the alpha CaMKII autophosphorylation-deficient mice, implying that hyperactivity does not occur in response to discrete novel stimuli. The present data suggest that the behavior of alpha CaMKII autophosphorylation-deficient mice cannot simply be described as a low anxiety phenotype. Instead it is suggested that alpha CaMKII autophosphorylation influences locomotor reactivity to novel environments that are potentially, but not necessarily threatening. (C) 2011 Elsevier Ltd. All rights reserved.