Li Shuo, Wang Laijian, Tie Xiaoxiu, Sohya Kazuhiro, Lin Xian, Kirkwood Alfredo, Jiang Bin
Guangdong Province Key Laboratory of Brain Function and Disease, Faculty of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080 China.
Mind/Brain Institute, Johns Hopkins University, Baltimore, Maryland 21218, and.
J Neurosci. 2017 Sep 27;37(39):9353-9360. doi: 10.1523/JNEUROSCI.0334-17.2017. Epub 2017 Aug 18.
LTP has been known to be a mechanism by which experience modifies synaptic responses in the neocortex. Visual deprivation in the form of dark exposure or dark rearing from birth enhances NMDAR-dependent LTP in layer 2/3 of visual cortex, a process often termed metaplasticity, which may involve changes in NMDAR subunit composition and function. However, the effects of reexposure to light after dark rearing from birth on LTP induction have not been explored. Here, we showed that the light exposure after dark rearing revealed a novel NMDAR independent form of LTP in the layer 2/3 pyramidal cells in visual cortex of mice of both sexes, which is dependent on mGluR5 activation and is associated with intracellular Ca rise, CaMKII activity, PKC activity, and intact protein synthesis. Moreover, the capacity to induce mGluR-dependent LTP is transient: it only occurs when mice of both sexes reared in the dark from birth are exposed to light for 10-12 h, and it does not occur in vision-experienced, male mice, even after prolonged exposure to dark. Thus, the mGluR5-LTP unmasked by short visual experience can only be observed after dark rearing but not after dark exposure. These results suggested that, as in hippocampus, in layer 2/3 of visual cortex, there is coexistence of two distinct activity-dependent systems of synaptic plasticity, NMDAR-LTP, and mGluR5-LTP. The mGluR5-LTP unmasked by short visual experience may play a critical role in the faster establishment of normal receptive field properties. LTP has been known to be a mechanism by which experience modifies synaptic responses in the neocortex. Visual deprivation in the form of dark exposure or dark rearing from birth enhances NMDAR-dependent LTP in layer 2/3 of visual cortex, a process often termed metaplasticity. NMDAR-dependent form of LTP in visual cortex has been well characterized. Here, we report that an NMDAR-independent form of LTP can be promoted by novel visual experience on dark-reared mice, characterized as dependent on intracellular Ca rise, PKC activity, and intact protein synthesis and also requires the activation of mGluR5. These findings suggest that, in layer 2/3 of visual cortex, as in hippocampus, there is coexistence of two distinct activity-dependent systems of synaptic plasticity.
长期增强作用（LTP）一直被认为是经验改变新皮层突触反应的一种机制。以出生后黑暗暴露或饲养的形式出现的视觉剥夺会增强视觉皮层第2/3层中依赖N-甲基-D-天冬氨酸受体（NMDAR）的LTP，这一过程通常被称为元可塑性，可能涉及NMDAR亚基组成和功能的变化。然而，出生后黑暗饲养后再暴露于光对LTP诱导的影响尚未得到研究。在这里，我们表明，黑暗饲养后的光照暴露揭示了一种新的不依赖NMDAR的LTP形式，存在于两性小鼠视觉皮层第2/3层的锥体细胞中，它依赖于代谢型谷氨酸受体5（mGluR5）的激活，并与细胞内钙离子升高、钙/钙调蛋白依赖性蛋白激酶II（CaMKII）活性、蛋白激酶C（PKC）活性以及完整的蛋白质合成有关。此外，诱导依赖mGluR的LTP的能力是短暂的：只有当出生后在黑暗中饲养的两性小鼠暴露于光下10 - 12小时时才会发生，而在有视觉经验的雄性小鼠中即使长时间暴露于黑暗中也不会发生。因此，短时间视觉经验揭示的mGluR蛋白5-LTP只能在黑暗饲养后观察到，而不能在黑暗暴露后观察到。这些结果表明，与海马体一样，在视觉皮层的第2/3层中，存在两种不同的依赖活动的突触可塑性系统，即NMDAR-LTP和mGluR5-LTP共存。短时间视觉经验揭示的mGluR5-LTP可能在更快建立正常感受野特性中起关键作用。长期增强作用（LTP）一直被认为是经验改变新皮层突触反应的一种机制。以出生后黑暗暴露或饲养的形式出现的视觉剥夺会增强视觉皮层第2/3层中依赖NMDAR的LTP，这一过程通常被称为元可塑性。视觉皮层中依赖NMDAR的LTP形式已经得到了很好的表征。在这里，我们报告说，新的视觉经验可以促进黑暗饲养小鼠中一种不依赖NMDAR的LTP形式，其特征是依赖于细胞内钙离子升高、PKC活性和完整的蛋白质合成，并且还需要mGluR5的激活。这些发现表明，在视觉皮层的第2/3层中，与海马体一样，存在两种不同的依赖活动的突触可塑性系统共存。
