Bidirectional, experience-dependent regulation of N-methyl-d-aspartate receptor subunit composition in the rat visual cortex during postnatal development

In the visual cortex, as elsewhere, N-methyl-d-aspartate receptors (NMDARs) play a critical role in triggering long-term, experience-dependent synaptic plasticity. Modifications of NMDAR subunit composition alter receptor function, and could have a large impact on the properties of synaptic plasticity. We have used immunoblot analysis to investigate the effects of age and visual experience on the expression of different NMDAR subunits in synaptoneurosomes prepared from rat visual cortices. NMDARs at birth are comprised of NR2B and NR1 subunits, and, over the first 5 postnatal weeks, there is a progressive inclusion of the NR2A subunit. Dark rearing from birth attenuates the developmental increase in NR2A. Levels of NR2A increase rapidly (in <2 hr) when dark-reared animals are exposed to light, and decrease gradually over the course of 3 to 4 days when animals are deprived of light. These data reveal that NMDAR subunit composition in the visual cortex is remarkably dynamic and bidirectionally regulated by sensory experience. We propose that NMDAR subunit regulation is a mechanism for experience-dependent modulation of synaptic plasticity in the visual cortex, and serves to maintain synaptic strength within an optimal dynamic range.

与其他脑区一致，视觉皮层中的N-甲基-D-天冬氨酸受体（N-methyl-d-aspartate receptors, NMDARs）在触发长期经验依赖性突触可塑性（synaptic plasticity）的过程中发挥关键作用。NMDAR亚基组成的修饰会改变受体功能，进而对突触可塑性的特性产生重大影响。本研究采用免疫印迹分析（immunoblot analysis），探究了年龄与视觉经验对大鼠视觉皮层制备的突触神经小体（synaptoneurosomes）中不同NMDAR亚基表达水平的影响。新生个体的NMDAR由NR2B与NR1亚基构成；在出生后的前5周内，NR2A亚基会逐步整合到受体复合物中。从出生即进行暗养（dark rearing）会削弱NR2A的发育性上调。当暗养动物暴露于光照环境时，NR2A的水平会在2小时内快速升高；而当动物被剥夺光照时，其NR2A水平则会在3至4天内逐渐下降。上述数据揭示，视觉皮层内的NMDAR亚基组成具有显著的动态性，并可双向响应感觉经验的调控。我们认为，NMDAR亚基的调控是视觉皮层中经验依赖性突触可塑性调节的一种机制，其作用在于将突触强度维持在最优动态范围内。