Lu Wei, Constantine-Paton Martha
Department of Biology, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
Neuron. 2004 Jul 22;43(2):237-49. doi: 10.1016/j.neuron.2004.06.031.
NMDA receptor (NMDAR)-mediated increases in AMPA receptor (AMPAR) currents are associated with long-term synaptic potentiation (LTP). Here, we provide evidence that similar changes occur in response to normal increases in sensory stimulation during development. Experiments discriminated between eye opening-induced and age-dependent changes in synaptic currents. At 6 hr after eye opening (AEO), a transient population of currents mediated by NR2B-rich NMDARs increase significantly, and silent synapses peak. Sustained increases in evoked and miniature AMPAR currents occur at 12 hr AEO. Significant changes in AMPAR:NMDAR evoked current ratios, contacts per axon, and inputs per cell are present at 24 hr AEO. The AMPAR current changes are those seen in vitro during NMDAR-dependent LTP. Here, they are a consequence of eye opening and are associated with a new wave of synaptic refinement. These data also suggest that new NR2B-rich NMDAR currents precede and may initiate this developmental synaptic potentiation and functional tuning.
N-甲基-D-天冬氨酸受体(NMDAR)介导的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体(AMPAR)电流增加与长期突触增强(LTP)相关。在此,我们提供证据表明,在发育过程中,响应于感觉刺激的正常增加会发生类似的变化。实验区分了睁眼诱导的和年龄依赖性的突触电流变化。在睁眼后6小时(AEO),由富含NR2B的NMDAR介导的瞬态电流群体显著增加,沉默突触达到峰值。在AEO 12小时时,诱发的和微小的AMPAR电流持续增加。在AEO 24小时时,AMPAR:NMDAR诱发电流比率、每个轴突的接触数和每个细胞的输入存在显著变化。AMPAR电流变化是在体外NMDAR依赖性LTP过程中观察到的那些变化。在此,它们是睁眼的结果,并且与新一轮的突触精细化相关。这些数据还表明,新的富含NR2B的NMDAR电流先于并可能启动这种发育性突触增强和功能调整。