Neuroscience Curriculum, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA.
Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA.
J Neurodev Disord. 2020 Oct 19;12(1):28. doi: 10.1186/s11689-020-09329-y.
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.
感觉处理缺陷在神经发育障碍患者中很常见。有一种假设认为，缺陷在下游的“更高”感觉区域可能更容易被检测到。缺乏母系遗传 Ube3a 等位基因表达的 Angelman 综合征（AS）小鼠模型在初级视觉皮层中存在突触功能和经验依赖性可塑性缺陷。因此，我们假设 AS 模型小鼠在下游更高视觉区域（HVAs）中存在视觉驱动的神经元反应缺陷。
在这里，我们使用内源信号光学成像和双光子钙成像来绘制对一系列刺激的初级视觉皮层和 HVAs 中视觉诱发的神经元活动图。
我们发现 HVAs 存在高度特异性缺陷。在野生型小鼠中，速度变化的漂移光栅会在 HVAs 中引起强烈反应，但在同窝的 AS 模型小鼠中没有观察到这种反应。使用双光子钙成像进行的进一步研究表明，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、刺激选择性皮质功能障碍的细胞基础。
检测下游或“更高”的电路可能为神经发育障碍的小鼠模型中的电路功能障碍提供更敏感的测量方法。
不适用。
