Persistent synapse loss induced by repetitive LTD in developing rat hippocampal neurons.
Persistent synapse loss induced by repetitive LTD in developing rat hippocampal neurons.
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DOI：
10.1371/journal.pone.0010390
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发表时间：
2010-04-28
期刊：
影响因子：
3.7
通讯作者：
Ogura A
中科院分区：
文献类型：
--
作者：
Shinoda Y;Tanaka T;Tominaga-Yoshino K;Ogura A
突触修剪是一种生理事件，在神经元发育过程中消除过多或不适当的突触以形成适当的突触连接。正常的神经发育需要适当的突触修剪。然而，突触修剪的机制尚不完全清楚。竞争环境下突触活动的强度被认为是突触修剪的选择性力量。长期抑制（LTD）是一种突触可塑性，表现出突触功效持续下降，并伴有树突棘的形态变化，包括短暂的回缩。重复诱导 LTD 已被证明会导致成熟神经元突触持续丧失。在这里，我们表明，多次（而非单次）LTD诱导会导致培养的大鼠发育海马神经元中树突突触数量持续减少。当通过应用（RS）-3,5-二羟基苯基甘氨酸（DHPG）（一种I组代谢型谷氨酸受体（mGluR）激动剂）在体外培养物中诱导LTD并以一天为间隔重复3次时，树突突触的数量显着减少。这种效果持续到三重LTD诱导后至少两周。突触数量的持续减少发生在近端树突，但不是远端树突，并且通过同时应用 I/II 组 mGluR 拮抗剂 (S)-a-甲基-4-羧基苯基甘氨酸 (MCPG) 来阻止突触数量的持续减少。总之，我们发现发育神经元中重复的 LTD 诱导会引发突触修剪，并有助于大鼠海马神经元突触数量的活动依赖性调节。
Synaptic pruning is a physiological event that eliminates excessive or inappropriate synapses to form proper synaptic connections during development of neurons. Appropriate synaptic pruning is required for normal neural development. However, the mechanism of synaptic pruning is not fully understood. Strength of synaptic activity under competitive circumstances is thought to act as a selective force for synaptic pruning. Long-term depression (LTD) is a synaptic plasticity showing persistent decreased synaptic efficacy, which is accompanied by morphological changes of dendritic spines including transient retraction. Repetitive induction of LTD has been shown to cause persistent loss of synapses in mature neurons. Here, we show that multiple, but not single, induction of LTD caused a persistent reduction in the number of dendritic synapses in cultured rat developing hippocampal neurons. When LTD was induced in 14 days in vitro cultures by application of (RS)-3,5-dihydroxyphenylglycine (DHPG), a group I metabotropic glutamate receptor (mGluR) agonist, and repeated three times with a one day interval, there was a significant decrease in the number of dendritic synapses. This effect continued up to at least two weeks after the triple LTD induction. The persistent reduction in synapse number occurred in the proximal dendrites, but not the distal dendrites, and was prevented by simultaneous application of the group I/II mGluR antagonist (S)-a-methyl-4-carboxyphenylglycine (MCPG). In conclusion, we found that repetitive LTD induction in developing neurons elicits synaptic pruning and contributes to activity-dependent regulation of synapse number in rat hippocampal neurons.
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