Circuit level defects in the developing neocortex of Fragile X mice.

Circuit level defects in the developing neocortex of Fragile X mice.
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DOI:
10.1038/nn.3415
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发表时间:
2013-07
影响因子:
25
通讯作者:
Portera-Cailliau, Carlos
Portera-Cailliau, Carlos
中科院分区:
医学1区
文献类型:
--
作者:
Goncalves, J. Tiago;Anstey, James E.;Golshani, Peyman;Portera-Cailliau, Carlos

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不同行为状态如何调节皮层网络动力学的细微变化可能会破坏正常的大脑功能,并成为神经精神疾病(包括脆性X综合征(FXS))的潜在症状。利用双光子钙成像和电生理技术记录了小鼠体感觉皮层自发神经元集合活动。未麻醉的Fmr1 - / -小鼠表现出异常高的新皮质网络活动同步,特别是在出生后的前两周。在全细胞记录中,Fmr1 - / -小鼠的神经元放电率高出3倍,表现为上/下状态(慢波睡眠,安静清醒),可能是由于在上状态时更高的放电概率。脑电图/钙成像联合实验证实,突变小鼠的神经元在睡眠期间具有异常高的放电和同步性。我们得出结论,在经验依赖可塑性的关键时期,FXS皮层网络以大脑状态依赖的方式过度兴奋。这些状态依赖的网络缺陷可以解释与FXS相关的智力、睡眠和感觉整合功能障碍。
Subtle alterations in how cortical network dynamics are modulated by different behavioral states could disrupt normal brain function and underlie symptoms of neuropsychiatric disorders, including fragile X syndrome (FXS). Using two-photon calcium imaging and electrophysiology we recorded spontaneous neuronal ensemble activity in mouse somatosensory cortex. Unanesthetized Fmr1–/– mice exhibited abnormally high synchrony of neocortical network activity, especially during the first two postnatal weeks. Neuronal firing rates were 3-fold higher in Fmr1–/– mice during whole-cell recordings manifesting Up/Down states (slow wave sleep, quiet wakefulness), likely due to a higher firing probability during Up states. Combined EEG/calcium imaging experiments confirmed that neurons in mutant mice have abnormally high firing and synchrony during sleep. We conclude that cortical networks in FXS are hyperexcitable in a brain state-dependent manner during a critical period for experience-dependent plasticity. These state-dependent network defects could explain the intellectual, sleep and sensory integration dysfunctions associated with FXS.
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