Neuroligin-1 loss is associated with reduced tenacity of excitatory synapses.
Neuroligin-1 loss is associated with reduced tenacity of excitatory synapses.
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DOI：
10.1371/journal.pone.0042314
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ziv NE
中科院分区：
文献类型：
--
作者：
Zeidan A;Ziv NE
神经连接蛋白(NLGNs)是突触后完整的膜细胞黏附分子，在哺乳动物中枢神经系统突触的形成、验证和成熟过程中发挥重要作用。鉴于它们在突触生命周期中的重要作用，可以预见，神经连接蛋白家族成员的缺失将影响突触组织的稳定性，最终影响单个突触连接的韧性和持久性。在这里，我们研究了NLGN-1的丢失是否以及在多大程度上影响了几个关键突触分子的动力学及其内容随着时间的推移在单个突触上的稳定性。荧光标记的突触后支架分子PSD-95、AMPA型谷氨酸受体亚单位GluA2和突触前囊泡分子SV2A在NLGN-1 KO小鼠和野生型(WT)鼠的原代皮质培养中表达，并用实时成像跟踪它们在各个突触8-12小时内含量的恒定。我们发现，NLGN-1的丢失与这些分子的突触内容的较大波动以及它们在单个突触的内容保存较差有关。此外，NLGN-1基因敲除小鼠的神经元突触更新率更高。最后，通过抑制自发的网络活动，NLGN-1基因敲除小鼠神经元中观察到的GluA2重分布率的增加被抵消。这些发现表明，NLGN-1的缺失与兴奋性突触组织的使用依赖性失稳有关，并提示在缺乏NLGN-1的情况下，兴奋性突触的韧性可能会受到一定程度的损害。
Neuroligins (Nlgns) are postsynaptic, integral membrane cell adhesion molecules that play important roles in the formation, validation, and maturation of synapses in the mammalian central nervous system. Given their prominent roles in the life cycle of synapses, it might be expected that the loss of neuroligin family members would affect the stability of synaptic organization, and ultimately, affect the tenacity and persistence of individual synaptic junctions. Here we examined whether and to what extent the loss of Nlgn-1 affects the dynamics of several key synaptic molecules and the constancy of their contents at individual synapses over time. Fluorescently tagged versions of the postsynaptic scaffold molecule PSD-95, the AMPA-type glutamate receptor subunit GluA2 and the presynaptic vesicle molecule SV2A were expressed in primary cortical cultures from Nlgn-1 KO mice and wild-type (WT) littermates, and live imaging was used to follow the constancy of their contents at individual synapses over periods of 8–12 hours. We found that the loss of Nlgn-1 was associated with larger fluctuations in the synaptic contents of these molecules and a poorer preservation of their contents at individual synapses. Furthermore, rates of synaptic turnover were somewhat greater in neurons from Nlgn-1 knockout mice. Finally, the increased GluA2 redistribution rates observed in neurons from Nlgn-1 knockout mice were negated by suppressing spontaneous network activity. These findings suggest that the loss of Nlgn-1 is associated with some use-dependent destabilization of excitatory synapse organization, and indicate that in the absence of Nlgn-1, the tenacity of excitatory synapses might be somewhat impaired.
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DOI：
10.1523/jneurosci.1042-04.2004
发表时间：
2004-06-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ashby MC;De La Rue SA;Ralph GS;Uney J;Collingridge GL;Henley JM
通讯作者：
Henley JM
影响因子：
15.9
作者：
Henley, Jeremy M.;Barker, Ellen A.;Glebov, Oleg O.
通讯作者：
Glebov, Oleg O.
影响因子：
5.3
作者：
Fisher-Lavie, Arava;Zeidan, Adel;Ziv, Noam E.
通讯作者：
Ziv, Noam E.
影响因子：
25
作者：
Groc, L;Heine, M;Choquet, D
通讯作者：
Choquet, D
DOI：
10.1073/pnas.1006946108
发表时间：
2011-02-15
影响因子：
11.1
作者：
Hoon, Mrinalini;Soykan, Tolga;Varoqueaux, Frederique
通讯作者：
Varoqueaux, Frederique