Department of Life Science, Pohang University of Science and Technology, Pohang, Gyungbuk 790-784, Korea.
Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4710-5. doi: 10.1073/pnas.1001084107. Epub 2010 Feb 22.
Despite considerable evidence for a critical role of neuroligin-1 in the specification of excitatory synapses, the cellular mechanisms and physiological roles of neuroligin-1 in mature neural circuits are poorly understood. In mutant mice deficient in neuroligin-1, or adult rats in which neuroligin-1 was depleted, we have found that neuroligin-1 stabilizes the NMDA receptors residing in the postsynaptic membrane of amygdala principal neurons, which allows for a normal range of NMDA receptor-mediated synaptic transmission. We observed marked decreases in NMDA receptor-mediated synaptic currents at afferent inputs to the amygdala of neuroligin-1 knockout mice. However, the knockout mice exhibited a significant impairment in spike-timing-dependent long-term potentiation (STD-LTP) at the thalamic but not the cortical inputs to the amygdala. Subsequent electrophysiological analyses indicated that STD-LTP in the cortical pathway is largely independent of activation of postsynaptic NMDA receptors. These findings suggest that neuroligin-1 can modulate, in a pathway-specific manner, synaptic plasticity in the amygdala circuits of adult animals, likely by regulating the abundance of postsynaptic NMDA receptors.
尽管有大量证据表明神经黏附素-1在兴奋性突触的特化中起着关键作用，但神经黏附素-1在成熟神经回路中的细胞机制和生理作用还知之甚少。在神经黏附素-1缺失的突变小鼠或神经黏附素-1耗尽的成年大鼠中，我们发现神经黏附素-1稳定了位于杏仁核主神经元突触后膜的 NMDA 受体，从而允许 NMDA 受体介导的突触传递在正常范围内。我们观察到神经黏附素-1敲除小鼠杏仁核传入输入的 NMDA 受体介导的突触电流明显减少。然而，敲除小鼠在丘脑但不在皮质输入到杏仁核的长时程增强（LTP）表现出显著的损伤。随后的电生理分析表明，皮质通路中的 STD-LTP 在很大程度上独立于突触后 NMDA 受体的激活。这些发现表明，神经黏附素-1可以以特定于通路的方式调节成年动物杏仁核回路中的突触可塑性，可能通过调节突触后 NMDA 受体的丰度来实现。
