NR2A在视觉皮层可塑性变化中起关键作用。
Obligatory role of NR2A for metaplasticity in visual cortex.
作者信息
Philpot Benjamin D, Cho Kathleen K A, Bear Mark F
机构信息
Curriculum in Neurobiology, Neuroscience Center, and Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, 105 Mason Farm Road, Chapel Hill, NC 27599, USA.
出版信息
Neuron. 2007 Feb 15;53(4):495-502. doi: 10.1016/j.neuron.2007.01.027.
Abstract
Light deprivation lowers the threshold for long-term depression (LTD) and long-term potentiation (LTP) in visual cortex by a process termed metaplasticity, but the mechanism is unknown. The decreased LTD/P threshold correlates with a decrease in the ratio of NR2A to NR2B subunits of cortical NMDA receptors (NMDARs) and a slowing of NMDAR-mediated excitatory postsynaptic currents (EPSCs). However, whether and how changes in NR2 subunit expression contribute to LTD and LTP have been controversial. In the present study, we used an NR2A knockout (KO) mouse to examine the role of this subunit in the experience-dependent modulation of NMDAR properties, LTD, and LTP. We found that deletion of NR2A abrogates the effects of visual experience on NMDAR EPSCs and prevents metaplasticity of LTP and LTD. These data support the hypothesis that experience-dependent changes in NR2A/B are functionally significant and yield a mechanism for an adjustable synaptic modification threshold in visual cortex.
摘要
光剥夺通过一种称为元可塑性的过程降低了视觉皮层中长时程抑制（LTD）和长时程增强（LTP）的阈值，但其机制尚不清楚。LTD/LTP阈值的降低与皮层N-甲基-D-天冬氨酸受体（NMDAR）的NR2A与NR2B亚基比率的降低以及NMDAR介导的兴奋性突触后电流（EPSC）的减慢相关。然而，NR2亚基表达的变化是否以及如何影响LTD和LTP一直存在争议。在本研究中，我们使用NR2A基因敲除（KO）小鼠来研究该亚基在依赖经验的NMDAR特性、LTD和LTP调节中的作用。我们发现，NR2A的缺失消除了视觉经验对NMDAR EPSC的影响，并阻止了LTP和LTD的元可塑性。这些数据支持了这样的假设，即NR2A/B中依赖经验的变化在功能上具有重要意义，并为视觉皮层中可调节的突触修饰阈值提供了一种机制。
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