Ehrlich Ingrid, Klein Matthew, Rumpel Simon, Malinow Roberto
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):4176-81. doi: 10.1073/pnas.0609307104. Epub 2007 Feb 27.
The activity-dependent regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors and the stabilization of synapses are critical to synaptic development and plasticity. One candidate molecule implicated in maturation, synaptic strengthening, and plasticity is PSD-95. Here we find that acute knockdown of PSD-95 in brain slice cultures by RNAi arrests the normal development of synaptic structure and function that is driven by spontaneous activity. Surprisingly, PSD-95 is not necessary for the induction and early expression of long-term potentiation (LTP). However, knockdown of PSD-95 leads to smaller increases in spine size after chemically induced LTP. Furthermore, although at this age spine turnover is normally low and LTP produces a transient increase, in cells with reduced PSD-95 spine turnover is high and remains increased after LTP. Taken together, our data support a model in which appropriate levels of PSD-95 are required for activity-dependent synapse stabilization after initial phases of synaptic potentiation.
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型谷氨酸受体的活性依赖性调节以及突触的稳定对于突触发育和可塑性至关重要。一种与成熟、突触增强和可塑性有关的候选分子是PSD-95。我们发现，通过RNA干扰在脑片培养物中急性敲低PSD-95会阻止由自发活动驱动的突触结构和功能的正常发育。令人惊讶的是，PSD-95对于长时程增强（LTP）的诱导和早期表达并非必需。然而，敲低PSD-95会导致化学诱导的LTP后棘突大小的增加较小。此外，虽然在这个年龄棘突更新通常较低，LTP会产生短暂增加，但在PSD-95减少的细胞中，棘突更新较高，并且在LTP后仍然增加。综上所述，我们的数据支持一种模型，即在突触增强的初始阶段之后，活性依赖性突触稳定需要适当水平的PSD-95。
