De Roo Mathias, Klauser Paul, Mendez Pablo, Poglia Lorenzo, Muller Dominique
University of Geneva Medical School, Department of Neurosciences, Centre Médical Universitaire, 1211 Genève 4, Switzerland.
Cereb Cortex. 2008 Jan;18(1):151-61. doi: 10.1093/cercor/bhm041. Epub 2007 May 20.
Development and remodeling of synaptic networks occurs through a continuous turnover of dendritic spines. However, the mechanisms that regulate the formation and stabilization of newly formed spines remain poorly understood. Here, we applied repetitive confocal imaging to hippocampal slice cultures to address these issues. We find that, although the turnover rate of protrusions progressively decreased during development, the process of stabilization of new spines remained comparable both in terms of time course and low level of efficacy. Irrespective of the developmental stage, most new protrusions were quickly eliminated, in particular filopodia, which only occasionally lead to the formation of stable dendritic spines. We also found that the stabilization of new protrusions was determined within a critical period of 24 h and that this coincided with an enlargement of the spine head and the expression of tagged PSD-95. Blockade of postsynaptic AMPA and NMDA receptors significantly reduced the capacity of new spines to express tagged PSD-95 and decreased their probability to be stabilized. These results suggest a model in which synaptic development is associated with an extensive, nonspecific growth of protrusions followed by stabilization of a few of them through a mechanism that involves activity-driven formation of a postsynaptic density.
突触网络的发育和重塑通过树突棘的持续更新而发生。然而，调节新形成棘突的形成和稳定的机制仍知之甚少。在这里，我们对海马切片培养物应用重复共聚焦成像来解决这些问题。我们发现，尽管在发育过程中突起的更新率逐渐降低，但新棘突的稳定过程在时间进程和低效率水平方面仍然相当。无论发育阶段如何，大多数新突起很快被消除，特别是丝状伪足，它们只是偶尔导致稳定的树突棘的形成。我们还发现，新突起的稳定在24小时的关键期内确定，这与棘突头部的扩大和标记的PSD-95的表达相吻合。阻断突触后AMPA和NMDA受体显著降低了新棘突表达标记的PSD-95的能力，并降低了它们被稳定的概率。这些结果提示了一个模型，其中突触发育与突起的广泛、非特异性生长相关，随后通过一种涉及活性驱动的突触后致密物形成的机制使其中一些突起稳定。
