Roberts Adam C, Díez-García Javier, Rodriguiz Ramona M, López Iciar Paula, Luján Rafael, Martínez-Turrillas Rebeca, Picó Esther, Henson Maile A, Bernardo Danilo R, Jarrett Thomas M, Clendeninn Dallis J, López-Mascaraque Laura, Feng Guoping, Lo Donald C, Wesseling John F, Wetsel William C, Philpot Benjamin D, Pérez-Otaño Isabel
Department of Cell and Molecular Physiology, Neuroscience Center, and Neurodevelopmental Disorders Research Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Neuron. 2009 Aug 13;63(3):342-56. doi: 10.1016/j.neuron.2009.06.016.
NR3A is the only NMDA receptor (NMDAR) subunit that downregulates sharply prior to the onset of sensitive periods for plasticity, yet the functional importance of this transient expression remains unknown. To investigate whether removal/replacement of juvenile NR3A-containing NMDARs is involved in experience-driven synapse maturation, we used a reversible transgenic system that prolonged NR3A expression in the forebrain. We found that removal of NR3A is required to develop strong NMDAR currents, full expression of long-term synaptic plasticity, a mature synaptic organization characterized by more synapses and larger postsynaptic densities, and the ability to form long-term memories. Deficits associated with prolonged NR3A were reversible, as late-onset suppression of transgene expression rescued both synaptic and memory impairments. Our results suggest that NR3A behaves as a molecular brake to prevent the premature strengthening and stabilization of excitatory synapses and that NR3A removal might thereby initiate critical stages of synapse maturation during early postnatal neural development.
NR3A是唯一一种在可塑性敏感时期开始之前急剧下调的N-甲基-D-天冬氨酸受体（NMDAR）亚基，然而这种短暂表达的功能重要性仍不清楚。为了研究去除/替换含幼年NR3A的NMDAR是否参与经验驱动的突触成熟，我们使用了一种可逆转基因系统来延长前脑中NR3A的表达。我们发现，要形成强大的NMDAR电流、充分表达长期突触可塑性、形成以更多突触和更大的突触后致密物为特征的成熟突触组织以及形成长期记忆的能力，就需要去除NR3A。与NR3A延长相关的缺陷是可逆的，因为转基因表达的晚期抑制挽救了突触和记忆损伤。我们的结果表明，NR3A起到分子制动器的作用，以防止兴奋性突触过早增强和稳定，并且NR3A的去除可能由此启动出生后早期神经发育期间突触成熟的关键阶段。
