Zuo Yi, Yang Guang, Kwon Elaine, Gan Wen-Biao
Skirball Institute, Department of Physiology and Neuroscience, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.
Nature. 2005 Jul 14;436(7048):261-5. doi: 10.1038/nature03715.
A substantial decrease in the number of synapses occurs in the mammalian brain from the late postnatal period until the end of life. Although experience plays an important role in modifying synaptic connectivity, its effect on this nearly lifelong synapse loss remains unknown. Here we used transcranial two-photon microscopy to visualize postsynaptic dendritic spines in layer I of the barrel cortex in transgenic mice expressing yellow fluorescent protein. We show that in young adolescent mice, long-term sensory deprivation through whisker trimming prevents net spine loss by preferentially reducing the rate of ongoing spine elimination, not by increasing the rate of spine formation. This effect of deprivation diminishes as animals mature but still persists in adulthood. Restoring sensory experience after adolescent deprivation accelerates spine elimination. Similar to sensory manipulation, the rate of spine elimination decreases after chronic blockade of NMDA (N-methyl-D-aspartate) receptors with the antagonist MK801, and accelerates after drug withdrawal. These studies of spine dynamics in the primary somatosensory cortex suggest that experience plays an important role in the net loss of synapses over most of an animal's lifespan, particularly during adolescence.
从出生后期直至生命结束，哺乳动物大脑中的突触数量会大幅减少。尽管经验在改变突触连接方面发挥着重要作用，但其对这种几乎贯穿一生的突触损失的影响仍不为人知。在此，我们利用经颅双光子显微镜对表达黄色荧光蛋白的转基因小鼠桶状皮质第I层中的突触后树突棘进行可视化观察。我们发现，在年轻的青春期小鼠中，通过修剪触须进行长期感觉剥夺可通过优先降低正在进行的树突棘消除速率而非增加树突棘形成速率来防止树突棘净损失。随着动物成熟，这种剥夺效应会减弱，但在成年期仍会持续存在。青春期剥夺后恢复感觉经验会加速树突棘消除。与感觉操纵类似，用拮抗剂MK801慢性阻断NMDA（N-甲基-D-天冬氨酸）受体后，树突棘消除速率会降低，而停药后则会加速。这些对初级体感皮质中树突棘动态变化的研究表明，经验在动物大部分生命周期的突触净损失中起着重要作用，尤其是在青春期。
