NgR1: A Tunable Sensor Regulating Memory Formation, Synaptic, and Dendritic Plasticity.
NgR1: A Tunable Sensor Regulating Memory Formation, Synaptic, and Dendritic Plasticity.
复制标题
DOI：
10.1093/cercor/bhw007
复制
发表时间：
2016-04
期刊：
影响因子：
--
通讯作者：
Olson L
中科院分区：
文献类型：
--
作者：
Karlsson TE;Smedfors G;Brodin AT;Åberg E;Mattsson A;Högbeck I;Wellfelt K;Josephson A;Brené S;Olson L
Nogo受体1(NgR1)在前脑神经元中表达，并在Nogo和其他配体的作用下介导神经生长抑制。神经元活动下调NgR1，而无法下调NgR1会损害长期记忆。我们对过度表达或缺乏NgR1的小鼠进行了一系列行为范式的研究，发现缺乏NgR1的小鼠运动行为和识别记忆受损，NgR1过度表达的小鼠顺序空间学习受损。我们还研究了NgR1在药物介导的致敏中的作用，发现重复暴露可卡因会导致NgR1过度表达的小鼠产生更强的运动反应，但限制了刻板印象的发展。这表明，NgR1调节的突触可塑性是形成刻板印象所必需的。体外磁共振成像和扩散张量成像分析NgR1过度表达的大脑没有发现任何重大变化。NGR1过表达导致成熟棘突密度和树突复杂性显著降低。NGR1的过表达也改变了可卡因对脊柱可塑性的影响。我们的结果表明，NGR1是结构突触可塑性和树突复杂性的负调节因子，并以脑区特异性的方式，突出了前扣带皮质作为记忆相关可塑性的关键区域。
Nogo receptor 1 (NgR1) is expressed in forebrain neurons and mediates nerve growth inhibition in response to Nogo and other ligands. Neuronal activity downregulates NgR1 and the inability to downregulate NgR1 impairs long-term memory. We investigated behavior in a serial behavioral paradigm in mice that overexpress or lack NgR1, finding impaired locomotor behavior and recognition memory in mice lacking NgR1 and impaired sequential spatial learning in NgR1 overexpressing mice. We also investigated a role for NgR1 in drug-mediated sensitization and found that repeated cocaine exposure caused stronger locomotor responses but limited development of stereotypies in NgR1 overexpressing mice. This suggests that NgR1-regulated synaptic plasticity is needed to develop stereotypies. Ex vivo magnetic resonance imaging and diffusion tensor imaging analyses of NgR1 overexpressing brains did not reveal any major alterations. NgR1 overexpression resulted in significantly reduced density of mature spines and dendritic complexity. NgR1 overexpression also altered cocaine-induced effects on spine plasticity. Our results show that NgR1 is a negative regulator of both structural synaptic plasticity and dendritic complexity in a brain region-specific manner, and highlight anterior cingulate cortex as a key area for memory-related plasticity.