Visual Experience-Dependent Oscillations and Underlying Circuit Connectivity Changes Are Impaired in Fmr1 KO Mice
Visual Experience-Dependent Oscillations and Underlying Circuit Connectivity Changes Are Impaired in Fmr1 KO Mice
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DOI：
10.1016/j.celrep.2020.03.050
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发表时间：
2020-04-07
期刊：
影响因子：
8.8
通讯作者：
Chubykin, Alexander A.
中科院分区：
文献类型：
--
作者：
Kissinger, Samuel T.;Wu, Qiuyu;Chubykin, Alexander A.
脆性 X 综合征 (FX) 是自闭症和智力障碍最常见的遗传形式，是一种与视觉感知学习缺陷相关的疾病。我们最近发现，感知体验可以通过小鼠初级视觉皮层（V1）的持续低频振荡来编码视觉熟悉度。在这里，我们将这种范例与多方面的实验方法相结合，以识别 FX 小鼠中这些振荡的神经生理学损伤。细胞外记录显示 FX 小鼠峰值振荡活动的持续时间较短、功率较低且频率较低。对细胞外记录的尖峰进行定向信息分析揭示了 FX 小鼠在感知体验后多层功能连接的差异。 Channelrhodopsin-2 辅助电路图谱 (CRACM) 揭示了在野生型 (WT) 小鼠（而非 FX 小鼠）中进行实验后，从 L5 锥体细胞到 L4 快速尖峰细胞的突触强度增加。这些结果表明，FX 中的视觉刺激熟悉度通过持续振荡进行差异编码，并确定可能导致这些变化的电路连接。
Fragile X syndrome (FX), the most common inherited form of autism and intellectual disability, is a condition associated with visual perceptual learning deficits. We recently discovered that perceptual experience can encode visual familiarity via persistent low-frequency oscillations in the mouse primary visual cortex (V1). Here, we combine this paradigm with a multifaceted experimental approach to identify neurophysiological impairments of these oscillations in FX mice. Extracellular recordings reveal shorter durations, lower power, and lower frequencies of peak oscillatory activity in FX mice. Directed information analysis of extracellularly recorded spikes reveals differences in functional connectivity from multiple layers in FX mice after the perceptual experience. Channelrhodopsin-2 assisted circuit mapping (CRACM) reveals increased synaptic strength from L5 pyramidal onto L4 fast-spiking cells after experience in wild-type (WT), but not FX, mice. These results suggest differential encoding of visual stimulus familiarity in FX via persistent oscillations and identify circuit connections that may underlie these changes.