Early postnatal plasticity in neocortex of Fmr1 knockout mice
Early postnatal plasticity in neocortex of Fmr1 knockout mice
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DOI：
10.1152/jn.00221.2006
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发表时间：
2006-10-01
影响因子：
2.5
通讯作者：
Vanderklish, Peter W.
中科院分区：
文献类型：
--
作者：
Desai, Niraj S.;Casimiro, Tanya M.;Vanderklish, Peter W.
脆性X综合征是由一个称为Fmr 1的X连锁基因缺陷引起的，其特征是异常的树突棘形态，新皮质中的棘比年龄匹配的对照组更长更细。使用Fmr 1基因敲除小鼠的研究表明，脊柱异常在生命的第一个月尤其明显，这表明发育可塑性的改变是与该综合征相关的一些行为表型的基础。为了解决这个问题，我们使用细胞内记录在新皮层切片从出生后早期的小鼠，以检查的影响，Fmr 1中断两种形式的可塑性活跃在发展过程中。其中之一，内在兴奋性的长时程增强，是内在的表达，需要mGluR 5激活。另一种是尖峰时间依赖的可塑性，它是突触性的表达，需要N-甲基-D-天冬氨酸受体激活。虽然内在可塑性在基因敲除小鼠中是正常的，但突触可塑性以一种不寻常和惊人的方式改变：长时程抑制是强大的，但长时程增强完全不存在。这些发现强调了这样一种观点，即Fmr 1对可塑性具有高度选择性的影响，并且出生后发育异常是这种疾病的重要组成部分。
Fragile X syndrome is produced by a defect in a single X-linked gene, called Fmr1, and is characterized by abnormal dendritic spine morphologies with spines that are longer and thinner in neocortex than those from age-matched controls. Studies using Fmr1 knockout mice indicate that spine abnormalities are especially pronounced in the first month of life, suggesting that altered developmental plasticity underlies some of the behavioral phenotypes associated with the syndrome. To address this issue, we used intracellular recordings in neocortical slices from early postnatal mice to examine the effects of Fmr1 disruption on two forms of plasticity active during development. One of these, long-term potentiation of intrinsic excitability, is intrinsic in expression and requires mGluR5 activation. The other, spike timing-dependent plasticity, is synaptic in expression and requires N-methyl-D-aspartate receptor activation. While intrinsic plasticity was normal in the knockout mice, synaptic plasticity was altered in an unusual and striking way: long-term depression was robust but long-term potentiation was entirely absent. These findings underscore the ideas that Fmr1 has highly selective effects on plasticity and that abnormal postnatal development is an important component of the disorder.