Sensory processing deficits are common in individuals with neurodevelopmental disorders. One hypothesis is that deficits may be more detectable in downstream, “higher” sensory areas. A mouse model of Angelman syndrome (AS), which lacks expression of the maternally inherited Ube3a allele, has deficits in synaptic function and experience-dependent plasticity in the primary visual cortex. Thus, we hypothesized that AS model mice have deficits in visually driven neuronal responsiveness in downstream higher visual areas (HVAs). Here, we used intrinsic signal optical imaging and two-photon calcium imaging to map visually evoked neuronal activity in the primary visual cortex and HVAs in response to an array of stimuli. We found a highly specific deficit in HVAs. Drifting gratings that changed speed caused a strong response in HVAs in wildtype mice, but this was not observed in littermate AS model mice. Further investigation with two-photon calcium imaging revealed the effect to be largely driven by aberrant responses of inhibitory interneurons, suggesting a cellular basis for higher level, stimulus-selective cortical dysfunction in AS. Assaying downstream, or “higher” circuitry may provide a more sensitive measure for circuit dysfunction in mouse models of neurodevelopmental disorders. Not applicable.

中文翻译：

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Angelman综合征小鼠模型中更高视觉区域表示的缺陷

感觉处理缺陷在患有神经发育障碍的个体中很常见。一种假设是缺陷在下游“更高”的感觉区域可能更容易检测到。Angelman 综合征 (AS) 的小鼠模型缺乏母系遗传的 Ube3a 等位基因的表达，在初级视觉皮层的突触功能和经验依赖性可塑性方面存在缺陷。因此，我们假设 AS 模型小鼠在下游更高的视觉区域 (HVA) 中存在视觉驱动的神经元反应缺陷。在这里，我们使用内在信号光学成像和双光子钙成像来映射初级视觉皮层和 HVA 中对一系列刺激的视觉诱发神经元活动。我们发现 HVA 存在高度特异性的缺陷。改变速度的漂移光栅在野生型小鼠的 HVA 中引起强烈反应，但这在同窝 AS 模型小鼠中未观察到。对双光子钙成像的进一步研究表明，这种影响主要是由抑制性中间神经元的异常反应驱动的，这表明 AS 中更高水平的刺激选择性皮质功能障碍的细胞基础。分析下游或“更高”的电路可能为神经发育障碍小鼠模型中的电路功能障碍提供更敏感的测量。不适用。或“更高”的电路可能为神经发育障碍小鼠模型中的电路功能障碍提供更灵敏的测量。不适用。或“更高”的电路可能为神经发育障碍小鼠模型中的电路功能障碍提供更灵敏的测量。不适用。