Effects of N-cadherin disruption on spine morphological dynamics.
Effects of N-cadherin disruption on spine morphological dynamics.
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DOI：
10.3389/neuro.03.001.2007
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发表时间：
2007
影响因子：
5.3
通讯作者：
Schuman EM
中科院分区：
文献类型：
--
作者：
Mysore SP;Tai CY;Schuman EM
突触的结构变化被认为是大脑中记忆编码的关键机制。最近的研究表明，树突棘动态行为的变化伴随着突触可塑性的双向变化，并且突触结构约束的破坏可能在树突棘可塑性中发挥机械作用。虽然 N-钙粘蛋白（一种关键的突触粘附分子）的长期破坏已被证明会改变脊柱形态，但人们对 N-钙粘蛋白对脊柱形态动力学的短期调节知之甚少。通过对培养的海马神经元进行延时共焦成像，我们检查了 AHAVD（一种已知会干扰 N-钙粘蛋白功能的肽）急性治疗后棘突结构变化的进展情况。我们对同一脊柱群中的快速和慢速时间尺度脊柱动力学（分别为分钟和小时）进行了表征。我们发现，N-钙粘蛋白破坏会导致脊柱运动增强、长度缩短，然后导致脊柱损失。结构效应伴随着功能连接的丧失。此外，我们证明 AHAVD 治疗引起的早期结构变化，即运动性增强和长度缩短，是后来脊柱命运的指标，即具有先前变化的脊柱更有可能随后丢失。因此，我们的结果揭示了 N-钙粘蛋白对突触结构的短期调节，并表明某些形式的形态动力学可能是后续刺激诱导的神经元网络重新布线的潜在读数。
Structural changes at synapses are thought to be a key mechanism for the encoding of memories in the brain. Recent studies have shown that changes in the dynamic behavior of dendritic spines accompany bidirectional changes in synaptic plasticity, and that the disruption of structural constraints at synapses may play a mechanistic role in spine plasticity. While the prolonged disruption of N-cadherin, a key synaptic adhesion molecule, has been shown to alter spine morphology, little is known about the short-term regulation of spine morphological dynamics by N-cadherin. With time-lapse, confocal imaging in cultured hippocampal neurons, we examined the progression of structural changes in spines following an acute treatment with AHAVD, a peptide known to interfere with the function of N-cadherin. We characterized fast and slow timescale spine dynamics (minutes and hours, respectively) in the same population of spines. We show that N-cadherin disruption leads to enhanced spine motility and reduced length, followed by spine loss. The structural effects are accompanied by a loss of functional connectivity. Further, we demonstrate that early structural changes induced by AHAVD treatment, namely enhanced motility and reduced length, are indicators for later spine fate, i.e., spines with the former changes are more likely to be subsequently lost. Our results thus reveal the short-term regulation of synaptic structure by N-cadherin and suggest that some forms of morphological dynamics may be potential readouts for subsequent, stimulus-induced rewiring in neuronal networks.
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