Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
Nat Commun. 2017 Jan 18;8:14077. doi: 10.1038/ncomms14077.
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 Mecp2 mice, a model of Rett syndrome. In response to learned maternal experience, Mecp2 females exhibited transient changes to cortical inhibitory networks typically associated with limited plasticity. Averting these changes in Mecp2 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 Mecp2. In this window of heightened sensitivity to sensory and social cues, Mecp2 mutations suppress adult plasticity independently from their effects on early development.
神经发育障碍的特点是生命早期突触连接异常，但经验依赖性可塑性的破坏如何导致成年认知和行为能力下降尚不清楚。在这里，我们发现，Mecp2 小鼠（雷特综合征的一种模型）的幼崽聚集行为和相关的听觉皮层可塑性受损。在对习得的母体经验的反应中，Mecp2 雌性表现出皮质抑制网络的短暂变化，这些变化通常与有限的可塑性相关。通过针对 GABA 能网络的遗传或药理学操作来避免这些变化，可恢复聚集行为。我们提出，幼崽聚集学习会引发听觉皮层中短暂的抑制性可塑性时期，而在 Mecp2 中这种时期被失调。在这个对感觉和社会线索高度敏感的窗口期，Mecp2 突变会抑制成年后的可塑性，而与它们对早期发育的影响无关。
