Structural basis of long-term potentiation in single dendritic spines

Structural basis of long-term potentiation in single dendritic spines
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DOI:
10.1038/nature02617
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发表时间:
2004-06-17
期刊:
影响因子:
64.8
通讯作者:
Kasai, H
Kasai, H
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Matsuzaki, M;Honkura, N;Kasai, H

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大脑皮层中锥体神经元的树突棘经历活动依赖性结构重塑(1-5),这被认为是学习和记忆的细胞基础(6)。结构重塑如何支持突触可塑性(4),5,如长时程增强(7),以及这种可塑性在个体脊柱水平上是否是输入特异性的仍然是未知的。我们使用海马CA 1锥体神经元单棘上笼状谷氨酸的双光子光解研究了长时程增强的结构基础(8)。在这里,我们表明,重复的量子样光释放(uncaging)的谷氨酸诱导快速和选择性扩大刺激的刺,是短暂的大蘑菇刺,但持续在小刺。脊髓增大与刺激突触处AMPA受体介导的电流增加相关,并依赖于NMDA受体、钙调蛋白和肌动蛋白聚合。长期脊柱增大也需要Ca 2 +/钙调蛋白依赖性蛋白激酶II。因此,我们的研究结果表明,脊柱个别遵循赫布的假设学习。他们进一步表明,小棘是长时程增强诱导的优先位点,而大棘可能代表长期记忆的物理痕迹。
Dendritic spines of pyramidal neurons in the cerebral cortex undergo activity-dependent structural remodelling(1-5) that has been proposed to be a cellular basis of learning and memory(6). How structural remodelling supports synaptic plasticity(4),5, such as long-term potentiation(7), and whether such plasticity is input-specific at the level of the individual spine has remained unknown. We investigated the structural basis of long-term potentiation using two-photon photolysis of caged glutamate at single spines of hippocampal CA1 pyramidal neurons(8). Here we show that repetitive quantum-like photorelease (uncaging) of glutamate induces a rapid and selective enlargement of stimulated spines that is transient in large mushroom spines but persistent in small spines. Spine enlargement is associated with an increase in AMPA-receptor-mediated currents at the stimulated synapse and is dependent on NMDA receptors, calmodulin and actin polymerization. Long-lasting spine enlargement also requires Ca2+/calmodulin-dependent protein kinase II. Our results thus indicate that spines individually follow Hebb's postulate for learning. They further suggest that small spines are preferential sites for long-term potentiation induction, whereas large spines might represent physical traces of long-term memory.