A structural basis for enhancement of long-term associative memory in single dendritic spines regulated by PKC
A structural basis for enhancement of long-term associative memory in single dendritic spines regulated by PKC
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DOI：
10.1073/pnas.0709311104
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发表时间：
2007-12-04
影响因子：
11.1
通讯作者：
Alkon, Daniel L.
中科院分区：
文献类型：
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作者：
Hongpaisan, Jarin;Alkon, Daniel L.
使用扫描共聚焦和电子显微镜形态测量，我们分析了单一的树突棘的CA 1锥体细胞在水迷宫训练大鼠与对照组的大脑中动脉。在完成所有训练的两天后，我们观察到蘑菇刺数量的记忆特异性增加-所有这些都使突触接触-但不是在丝状伪足或薄刺或薄刺的数量，如在扫描共聚焦和电子显微镜图像中的双盲协议所量化的。这种记忆特异性的蘑菇刺数量的增加被PKC激活剂和候选阿尔茨海默病治疗剂苔藓抑素增强，被PKC α-同工酶阻断剂Ro 31-8220阻断，并伴随着“穿孔”突触后密度的数量增加，突触前囊泡的数量增加，以及与蘑菇刺相关的双突触前终扣的发生增加。这些和其他共焦成像免疫组化结果在这里描述的涉及PKC底物表明，个别蘑菇刺提供结构存储网站的长期联想记忆和网站的记忆特异性突触发生，涉及PKC调节的脊柱形状的变化，以及PKC调节的前和突触后超微结构的变化。
Using both scanning confocal and electron microscopic morphometric measurements, we analyzed single dendritic spines of CA1 pyramidal cells in the hippocampi of water maze-trained rats vs. controls. Two days after completion of all training, we observed a memory-specific increase in the number of mushroom spines-all of which make synaptic contacts-but not in the numbers of filopodia or stubby or thin spines, as quantified with double-blind protocols in both scanning confocal and electron microscopic images. This memory-specific increase of mushroom spine number was enhanced by the PKC activator and candidate Alzheimer's disease therapeutic bryostatin, blocked by the PKC alpha-isozyme blocker Ro 31-8220, and accompanied by increases in the number of "perforated" postsynaptic densities, increased numbers of presynaptic vesicles, and the increased occurrence of double-synapse presynaptic boutons associated with the mushroom spines. These and other confocally imaged immunohistochemical results described here involving PKC substrates indicate that individual mushroom spines provide structural storage sites for long-term associative memory and sites for memory-specific synaptogenesis that involve PKC-regulated changes of spine shape, as well as PKC-regulated changes of pre- and postsynaptic ultrastructure.