Impermanence of dendritic spines in live adult CA1 hippocampus.
Impermanence of dendritic spines in live adult CA1 hippocampus.
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DOI：
10.1038/nature14467
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发表时间：
2015-07-30
期刊：
影响因子：
64.8
通讯作者：
Schnitzer MJ
中科院分区：
文献类型：
--
作者：
Attardo A;Fitzgerald JE;Schnitzer MJ
哺乳动物海马体对于情景记忆的形成至关重要，并且在成年小鼠中短暂地保留信息约3-4周，在人类中保留时间更长。虽然神经科学家普遍认为神经突触是信息存储的基本场所，但没有直接证据表明海马突触的持续时间与海马依赖记忆的持续时间相当。在这里，我们测试了海马突触的寿命与海马记忆寿命相匹配的预测。通过在活体小鼠海马CA 1区使用延时双光子显微内窥镜，我们监测了锥体神经元基底树突棘的周转动力学，突触后结构的周转动力学被认为反映了兴奋性突触连接。引人注目的是，CA 1脊髓周转动力学与以前在新皮层中看到的明显不同。数学建模显示，数据与平均寿命约1-2周的单个棘群的动力学模型最匹配。这意味着在约2-3倍的时间间隔内约100%的周转，突触连接模式几乎完全消失。虽然NMDA受体阻滞剂稳定了新皮层的棘，但在CA 1中，它短暂地增加了棘丢失的速率，从而降低了棘密度。这些结果表明，成人新皮层和海马锥体神经元有不同的模式的脊柱调节和定量支持的想法，即短暂的海马依赖的记忆直接反映了周转动力学的海马突触。
Mammalian hippocampus is crucial for episodic memory formation and transiently retains information for ~3–4 weeks in adult mice and longer in humans. Although neuroscientists widely believe neural synapses are elemental sites of information storage, there has been no direct evidence hippocampal synapses persist for time intervals commensurate with the duration of hippocampal-dependent memory. Here we tested the prediction that the lifetimes of hippocampal synapses match the longevity of hippocampal memory. By using time-lapse two-photon microendoscopy in the CA1 hippocampal area of live mice, we monitored the turnover dynamics of pyramidal neurons’ basal dendritic spines, post-synaptic structures whose turnover dynamics are thought to reflect those of excitatory synaptic connections. Strikingly, CA1 spine turnover dynamics differed sharply from that seen previously in neocortex. Mathematical modeling revealed that the data best matched kinetic models with a single population of spines of mean lifetime ~1–2 weeks. This implies ~100% turnover in ~2–3 times this interval, a near full erasure of the synaptic connectivity pattern. Although NMDA receptor blockade stabilizes spines in neocortex, in CA1 it transiently increased the rate of spine loss and thus lowered spine density. These results reveal that adult neocortical and hippocampal pyramidal neurons have divergent patterns of spine regulation and quantitatively support the idea that the transience of hippocampal-dependent memory directly reflects the turnover dynamics of hippocampal synapses.