Tang Y P, Shimizu E, Dube G R, Rampon C, Kerchner G A, Zhuo M, Liu G, Tsien J Z
Department of Molecular Biology, Princeton University, New Jersey 08544-1014, USA.
Nature. 1999 Sep 2;401(6748):63-9. doi: 10.1038/43432.
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, 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.
赫布法则（1949年）指出，学习和记忆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巧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（一种突触巧合探测器）作为记忆形成的分级开关，NMDA受体增强的信号检测应该会增强学习和记忆。在这里，我们表明，转基因小鼠前脑中NMDA受体2B（NR2B）的过表达导致NMDA受体的激活增强，促进了对10 - 100赫兹刺激的突触增强。这些小鼠在各种行为任务中表现出卓越的学习和记忆能力，表明NR2B在控制可塑性和记忆形成的年龄依赖性阈值方面至关重要。因此，NMDA受体依赖性的突触效能改变代表了联想学习和记忆的统一机制。我们的结果表明，在哺乳动物中通过基因增强诸如智力和记忆等心理和认知属性是可行的。
