Corlew Rebekah, Wang Yun, Ghermazien Haben, Erisir Alev, Philpot Benjamin D
Curriculum in Neurobiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
J Neurosci. 2007 Sep 12;27(37):9835-45. doi: 10.1523/JNEUROSCI.5494-06.2007.
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.
许多形式的学习和记忆以及感觉系统感受野可塑性都需要N-甲基-D-天冬氨酸受体（NMDAR）的激活，然而在整个皮层发育过程中，突触前和突触后NMDAR的相对作用仍不清楚。在这里，我们证明了新皮层中功能性突触前NMDAR在发育过程中迅速丧失。突触前NMDAR增强了幼鼠（出生后第20天之前，即P20）视皮层锥体细胞突触处的神经递质释放，但在感受野可塑性关键期开始后（>P23），它们没有明显作用。免疫电子显微镜显示，突触前NMDAR功能丧失可能部分归因于突触前NMDAR的患病率降低了50%。与观察到的突触前NMDAR功能丧失同时发生的是，时间依赖性长时程抑制（tLTD）机制发生了突然变化。在关键期开始前诱导tLTD需要激活突触前而非突触后NMDAR，而在老年小鼠中诱导tLTD则需要激活突触后NMDAR。通过证明突触前和突触后NMDAR都有助于诱导突触可塑性，且它们的相对作用在发育过程中发生变化，我们的研究结果定义了新皮层回路中突触可塑性的一种新的、可能也是普遍的特性。
