Age-dependent and selective impairment of long-term potentiation in the anterior piriform cortex of mice lacking the fragile X mental retardation protein
Age-dependent and selective impairment of long-term potentiation in the anterior piriform cortex of mice lacking the fragile X mental retardation protein
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DOI：
10.1523/jneurosci.2638-05.2005
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发表时间：
2005-10-12
影响因子：
5.3
通讯作者：
du Hoffmann, J
中科院分区：
文献类型：
--
作者：
Larson, J;Jessen, RE;du Hoffmann, J
在缺乏脆性X智力低下蛋白（FMRP）的小鼠（脆性X智力低下综合征的模型）中研究了突触功能和可塑性。在梨状（嗅觉）前皮质切片中研究了关联连接，在海马切片中研究了Schaffer连合突触。将缺乏FMRP的敲除（KO）小鼠与同源C57 BL/6 J野生型（WT）对照进行比较。与WT小鼠相比，KO小鼠的嗅觉皮层或海马的输入-输出曲线和成对脉冲可塑性没有显著改变。在6月龄KO小鼠中，由θ爆发刺激诱导的前梨状皮质中的长时程增强（LTP）是正常< 6 months but was impaired in KO mice aged >的。LTP的缺陷在6-12月龄的小鼠中是显著的，并且在12-18月龄的小鼠中更明显。无论是否在存在或不存在GABA（A）受体阻滞剂的情况下诱导LTP，WT和KO小鼠之间都存在类似的差异。KO小鼠对模式化爆发刺激的突触后反应显示LTP受损，与WT小鼠无显著差异，表明LTP缺陷不是由电路特性改变引起的。在任何年龄的WT和KO小鼠中均未观察到海马LTP的差异。结果表明，FMRP缺陷与年龄依赖性和区域选择性损害的长期突触可塑性。
Synaptic function and plasticity were studied in mice lacking the fragile X mental retardation protein (FMRP), a model for the fragile X mental retardation syndrome. Associational connections were studied in slices of anterior piriform (olfactory) cortex, and Schaffer-commissural synapses were studied in slices of hippocampus. Knock-out ( KO) mice lacking FMRP were compared with congenic C57BL/6J wild-type (WT) controls. Input-output curves and paired-pulse plasticity were not significantly altered in KO compared with WT mice in either the olfactory cortex or hippocampus. Long-term potentiation (LTP) induced by theta burst stimulation in the anterior piriform cortex was normal in KO mice aged < 6 months but was impaired in KO mice aged > 6 months. The deficit in LTP was significant in mice aged 6-12 months and more pronounced in mice aged 12-18 months. Similar differences between WT and KO mice were seen whether LTP was induced in the presence or absence of a GABA(A) receptor blocker. Postsynaptic responses to patterned burst stimulation in KO mice showing impaired LTP were not significantly different from those in WT mice, suggesting that the LTP deficit was not caused by alterations in circuit properties. No differences in hippocampal LTP were observed in WT and KO mice at any ages. The results indicate that FMRP deficiency is associated with an age-dependent and region-selective impairment in long-term synaptic plasticity.