Genetic enhancement of learning and memory in mice
Genetic enhancement of learning and memory in mice
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DOI：
10.1038/43432
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发表时间：
1999-09-02
期刊：
影响因子：
64.8
通讯作者：
Tsien, JZ
中科院分区：
文献类型：
--
作者：
Tang, YP;Shimizu, E;Tsien, JZ
Hebb的规则(1949)指出，学习和记忆是基于同时活跃的神经元之间突触强度的改变。这意味着增强的突触符合检测将导致更好的学习和记忆。如果NMDA(N-甲基-D-天冬氨酸)受体，一个突触符合检测器(1-4)，作为记忆形成的分级开关，那么NMDA受体增强的信号检测应该会增强学习和记忆。在这里，我们证明了NMDA受体2B(NR2B)在转基因小鼠的前脑中的过度表达导致NMDA受体的激活增强，从而促进了突触对10-100赫兹刺激的反应。这些小鼠在各种行为任务中表现出优越的学习和记忆能力，表明NR2B在控制年龄相关的可塑性和记忆形成阈值方面至关重要。因此，NMDA受体依赖的突触效能修饰代表了联想学习和记忆的统一机制。我们的结果表明，对哺乳动物的智力和记忆等智力和认知属性进行遗传增强是可行的。
Hebb's rule (1949) states that learning and memory are based on modifications of synaptic strength among neurons that are simultaneously active. This implies that enhanced synaptic coincidence detection would lead to better learning and memory. If the NMDA (N-methyl-D-aspartate) receptor, a synaptic coincidence detector(1-4), acts as a graded switch for memory formation, enhanced signal detection by NMDA receptors should enhance learning and memory. Here we show that overexpression of NMDA receptor 2B (NR2B) in the forebrains of transgenic mice leads to enhanced activation of NMDA receptors, facilitating synaptic potentiation in response to stimulation at 10-100 Hz. These mice exhibit superior ability in learning and memory in various behavioural tasks, showing that NR2B is critical in gating the age-dependent threshold for plasticity and memory formation. NMDA-receptor-dependent modifications of synaptic efficacy, therefore, represent a unifying mechanism for associative learning and memory. Our results suggest that genetic enhancement of mental and cognitive attributes such as intelligence and memory in mammals is feasible.