Developmental switch in the contribution of presynaptic and postsynaptic NMDA receptors to long-term depression
Developmental switch in the contribution of presynaptic and postsynaptic NMDA receptors to long-term depression
复制标题
DOI：
10.1523/jneurosci.5494-06.2007
复制
发表时间：
2007-09-12
影响因子：
5.3
通讯作者：
Philpot, Benjamin D.
中科院分区：
文献类型：
--
作者：
Corlew, Rebekah;Wang, Yun;Philpot, Benjamin D.
NMDA受体（NMDAR）激活是许多形式的学习和记忆以及感觉系统感受野可塑性所必需的，但突触前和突触后NMDAR对皮层发育的相对贡献仍然未知。在这里，我们证明了一个快速发展的功能性突触前NMDARs在新皮层的损失。突触前NMDAR增强幼年小鼠[出生后20天（P20）前]视皮层锥体细胞上突触处的神经递质释放，但在感受野可塑性的关键期开始后（> P23），它们没有明显的作用。免疫电镜显示，突触前NMDAR功能的丧失可能部分归因于突触前NMDAR患病率降低50%。与观察到的突触前NMDAR功能丧失同时，时间依赖性长期抑郁（tLTD）的机制也发生了突然变化。在关键期开始之前诱导tLTD需要激活突触前而不是突触后NMDAR，而在老年小鼠中诱导tLTD需要激活突触后NMDAR。通过证明突触前和突触后NMDAR有助于诱导突触可塑性，并且它们的相对作用随着发育而改变，我们的研究结果定义了一种新的，也许是一般的，新兴皮层回路中突触可塑性的特性。
NMDA receptor (NMDAR) activation is required for many forms of learning and memory as well as sensory system receptive field plasticity, yet the relative contribution of presynaptic and postsynaptic NMDARs over cortical development remains unknown. Here we demonstrate a rapid developmental loss of functional presynaptic NMDARs in the neocortex. Presynaptic NMDARs enhance neurotransmitter release at synapses onto visual cortex pyramidal cells in young mice [before postnatal day 20 (P20)], but they have no apparent effect after the onset of the critical period for receptive field plasticity (> P23). Immunoelectron microscopy revealed that the loss of presynaptic NMDAR function is likely attributable in part to a 50% reduction in the prevalence of presynaptic NMDARs. Coincident with the observed loss of presynaptic NMDAR function, there is an abrupt change in the mechanisms of timing-dependent long-term depression (tLTD). Induction of tLTD before the onset of the critical period requires activation of presynaptic but not postsynaptic NMDARs, whereas the induction of tLTD in older mice requires activation of postsynaptic NMDARs. By demonstrating that both presynaptic and postsynaptic NMDARs contribute to the induction of synaptic plasticity and that their relative roles shift over development, our findings define a novel, and perhaps general, property of synaptic plasticity in emerging cortical circuits.