PSD-95 is required for activity-driven synapse stabilization
PSD-95 is required for activity-driven synapse stabilization
复制标题
DOI：
10.1073/pnas.0609307104
复制
发表时间：
2007-03-06
影响因子：
11.1
通讯作者：
Malinow, Roberto
中科院分区：
文献类型：
--
作者：
Ehrlich, Ingrid;Klein, Matthew;Malinow, Roberto
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型谷氨酸受体的活动依赖性调节以及突触的稳定对突触发育和可塑性至关重要。一种与成熟、突触强化和可塑性有关的候选分子是PSD - 95。在此我们发现，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对长时程增强（LTP）的诱导和早期表达不是必需的。然而，在化学诱导LTP后，敲低PSD - 95会导致树突棘尺寸的增加幅度变小。此外，尽管在这个阶段树突棘的周转通常较低，且LTP会产生短暂的增加，但在PSD - 95减少的细胞中，树突棘周转较高，且在LTP后仍然保持较高水平。综上所述，我们的数据支持这样一种模型，即突触增强的初始阶段之后，适当水平的PSD - 95是活动依赖性突触稳定所必需的。
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.