Dumas Theodore C
Institute of Neuroscience, 1254 University of Oregon, Eugene, OR 97403-1254, USA.
Prog Neurobiol. 2005 Jun;76(3):189-211. doi: 10.1016/j.pneurobio.2005.08.002.
N-methyl-D-aspartate receptors (NMDARs) act as molecular coincidence detectors and allow for association or dissociation between pre- and postsynaptic neurons. NMDA receptors are central to remodeling of synaptic connections during postnatal development and associative learning abilities in adults. The ability to remodel neural networks is altered during postnatal development, possibly due to a change in the composition of NMDARs. That is, as forebrain systems (and cerebellum) develop, synaptic NR2B-containing NMDARs (NR2B-NMDARs) are replaced by NR2A-containing NMDARs (NR2A-NMDARs) and NR2B-NMDARs move to extrasynaptic sites. During the initial phase of the switch, synapses contain both NR2A- and NR2B-NMDARs and both long-term potentiation and long-term depression are enhanced. As NMDAR subunit expression decreases and NR2A-NMDARs come to predominate in the synapse, channel function and synaptic plasticity are reduced, and remodeling ability dissipates. The end result is a balance of plasticity and stability that is optimal for information processing and storage. Associative learning abilities involving different sensory modalities emerge sequentially, in accordance with synaptic maturation in related cortical and underlying brain structures. Thus, developmental alterations in NMDAR composition that occur at different ages in various brain structures may explain the protracted nature of the maturation of various associative learning abilities.
N-甲基-D-天冬氨酸受体（NMDARs）作为分子重合探测器，允许突触前和突触后神经元之间发生关联或解离。NMDA受体对于出生后发育期间突触连接的重塑以及成年人的联想学习能力至关重要。神经网络重塑能力在出生后发育过程中会发生改变，这可能是由于NMDARs组成的变化所致。也就是说，随着前脑系统（和小脑）的发育，含NR2B的突触NMDARs（NR2B-NMDARs）被含NR2A的NMDARs（NR2A-NMDARs）所取代，并且NR2B-NMDARs转移到突触外位点。在转换的初始阶段，突触同时包含NR2A-和NR2B-NMDARs，长时程增强和长时程抑制均增强。随着NMDAR亚基表达减少且NR2A-NMDARs在突触中占主导地位，通道功能和突触可塑性降低，重塑能力消失。最终结果是可塑性和稳定性达到平衡，这对于信息处理和存储而言是最佳的。涉及不同感觉模态的联想学习能力会根据相关皮层和基础脑结构中的突触成熟情况依次出现。因此，在不同年龄于各种脑结构中发生的NMDAR组成的发育性改变可能解释了各种联想学习能力成熟的漫长特性。
