MECP2 regulates cortical plasticity underlying a learned behaviour in adult female mice.
MECP2 regulates cortical plasticity underlying a learned behaviour in adult female mice.
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MECP2调节成年雌性小鼠学习的基本行为的皮质可塑性。
DOI：
10.1038/ncomms14077
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发表时间：
2017-01-18
影响因子：
16.6
通讯作者：
Shea SD
中科院分区：
文献类型：
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作者：
Krishnan K;Lau BY;Ewall G;Huang ZJ;Shea SD
神经发育障碍的特点是在生命早期不适当的突触连接，但经验依赖性可塑性的破坏如何导致成年后的认知和行为下降尚不清楚。在这里，我们表明，幼崽聚集行为和相关的听觉皮层可塑性受损的雌性Mecp2het小鼠，Rett综合征的模型。在响应学习的母亲的经验，Mecp2het女性表现出短暂的变化，皮质抑制网络通常与有限的可塑性。通过针对GABA能网络的遗传或药理学操作来避免Mecp2het中的这些变化，恢复了聚集行为。我们建议，小狗收集学习触发一个短暂的时期，在听觉皮层的抑制可塑性，是失调的Mecp2het。在这个对感官和社会线索高度敏感的窗口中，Mecp2突变抑制了成人可塑性，而与其对早期发育的影响无关。Rett综合征与发育早期开始的突触连接受损有关。在这里，作者在Mecp2杂合子雌性小鼠中显示，Rett综合征的模型，在成年期，与学习母性行为相关的听觉皮层可塑性也受损。
Neurodevelopmental disorders are marked by inappropriate synaptic connectivity early in life, but how disruption of experience-dependent plasticity contributes to cognitive and behavioural decline in adulthood is unclear. Here we show that pup gathering behaviour and associated auditory cortical plasticity are impaired in female Mecp2het mice, a model of Rett syndrome. In response to learned maternal experience, Mecp2het females exhibited transient changes to cortical inhibitory networks typically associated with limited plasticity. Averting these changes in Mecp2het through genetic or pharmacological manipulations targeting the GABAergic network restored gathering behaviour. We propose that pup gathering learning triggers a transient epoch of inhibitory plasticity in auditory cortex that is dysregulated in Mecp2het. In this window of heightened sensitivity to sensory and social cues, Mecp2 mutations suppress adult plasticity independently from their effects on early development. Rett syndrome is associated with impaired synaptic connectivity beginning in early development. Here the authors show in female mice heterozygous for Mecp2, a model of Rett syndrome, that during adulthood, auditory cortex plasticity associated with a learned maternal behaviour is also impaired.