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FMR1 基因敲除小鼠的桶状皮层中,关键期可塑性被破坏。

Critical period plasticity is disrupted in the barrel cortex of FMR1 knockout mice.

机构信息

Department of Physiology, Northwestern University Feinberg School of Medicine, 303 E Chicago Avenue, Chicago, IL 60611, USA.

出版信息

Neuron. 2010 Feb 11;65(3):385-98. doi: 10.1016/j.neuron.2010.01.024.

Abstract

Alterations in sensory processing constitute prominent symptoms of fragile X syndrome; however, little is known about how disrupted synaptic and circuit development in sensory cortex contributes to these deficits. To investigate how the loss of fragile X mental retardation protein (FMRP) impacts the development of cortical synapses, we examined excitatory thalamocortical synapses in somatosensory cortex during the perinatal critical period in Fmr1 knockout mice. FMRP ablation resulted in dysregulation of glutamatergic signaling maturation. The fraction of silent synapses persisting to later developmental times was increased; there was a temporal delay in the window for synaptic plasticity, while other forms of developmental plasticity were not altered in Fmr1 knockout mice. Our results indicate that FMRP is required for the normal developmental progression of synaptic maturation, and loss of this important RNA binding protein impacts the timing of the critical period for layer IV synaptic plasticity.

摘要

感觉处理的改变构成了脆性 X 综合征的突出症状;然而,对于感觉皮层中突触和回路发育的破坏如何导致这些缺陷知之甚少。为了研究脆性 X 智力迟钝蛋白 (FMRP) 的缺失如何影响皮质突触的发育,我们在 Fmr1 敲除小鼠的感觉皮层围产期关键期检查了兴奋性丘脑皮质突触。FMRP 缺失导致谷氨酸能信号转导成熟失调。持续到后期发育时间的沉默突触比例增加;突触可塑性的窗口存在时间延迟,而 Fmr1 敲除小鼠的其他形式的发育可塑性没有改变。我们的结果表明,FMRP 是突触成熟正常发育进程所必需的,这种重要的 RNA 结合蛋白的缺失会影响 IV 层突触可塑性的关键期的时间。

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