Yasumatsu Nobuaki, Matsuzaki Masanori, Miyazaki Takashi, Noguchi Jun, Kasai Haruo
Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Neurosci. 2008 Dec 10;28(50):13592-608. doi: 10.1523/JNEUROSCI.0603-08.2008.
Long-term potentiation of synapse strength requires enlargement of dendritic spines on cerebral pyramidal neurons. Long-term depression is linked to spine shrinkage. Indeed, spines are dynamic structures: they form, change their shapes and volumes, or can disappear in the space of hours. Do all such changes result from synaptic activity, or do some changes result from intrinsic processes? How do enlargement and shrinkage of spines relate to elimination and generation of spines, and how do these processes contribute to the stationary distribution of spine volumes? To answer these questions, we recorded the volumes of many individual spines daily for several days using two-photon imaging of CA1 pyramidal neurons in cultured slices of rat hippocampus between postnatal days 17 and 23. With normal synaptic transmission, spines often changed volume or were created or eliminated, thereby showing activity-dependent plasticity. However, we found that spines changed volume even after we blocked synaptic activity, reflecting a native instability of these small structures over the long term. Such "intrinsic fluctuations" showed unique dependence on spine volume. A mathematical model constructed from these data and the theory of random fluctuations explains population behaviors of spines, such as rates of elimination and generation, stationary distribution of volumes, and the long-term persistence of large spines. Our study finds that generation and elimination of spines are more prevalent than previously believed, and spine volume shows significant correlation with its age and life expectancy. The population dynamics of spines also predict key psychological features of memory.
突触强度的长期增强需要大脑锥体神经元上树突棘的增大。长期抑制与树突棘萎缩有关。实际上，树突棘是动态结构：它们会形成、改变形状和体积，或者在数小时内消失。所有这些变化都是由突触活动引起的吗？还是有些变化是由内在过程导致的？树突棘的增大和缩小如何与树突棘的消除和生成相关联？这些过程又是如何促成树突棘体积的稳定分布的？为了回答这些问题，我们在出生后第17至23天的大鼠海马体培养切片中，使用双光子成像技术，连续数天每天记录许多单个树突棘的体积。在正常突触传递情况下，树突棘经常改变体积，或者被创建或消除，从而表现出活动依赖性可塑性。然而，我们发现即使在阻断突触活动后，树突棘仍会改变体积，这反映了这些小结构长期存在的内在不稳定性。这种“内在波动”对树突棘体积表现出独特的依赖性。基于这些数据和随机波动理论构建的数学模型解释了树突棘的群体行为，如消除和生成速率、体积的稳定分布以及大树突棘的长期持续性。我们的研究发现，树突棘的生成和消除比之前认为的更为普遍，并且树突棘体积与其年龄和寿命存在显著相关性。树突棘的群体动态也预测了记忆的关键心理特征。
