Wallace Michael L, van Woerden Geeske M, Elgersma Ype, Smith Spencer L, Philpot Benjamin D
Curriculum in Neurobiology, University of North Carolina, Chapel Hill, North Carolina.
Department of Neuroscience, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
J Neurophysiol. 2017 Jul 1;118(1):634-646. doi: 10.1152/jn.00618.2016. Epub 2017 May 3.
Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of the maternally inherited allele of mice recapitulate major features of AS in humans and allow conditional reinstatement of maternal with the expression of Cre recombinase. We have recently shown that AS model mice exhibit reduced inhibitory drive onto layer (L)2/3 pyramidal neurons of visual cortex, which contributes to a synaptic excitatory/inhibitory imbalance. However, it remains unclear how this loss of inhibitory drive affects neural circuits in vivo. Here we examined visual cortical response properties in individual neurons to explore the consequences of loss on intact cortical circuits and processing. Using in vivo patch-clamp electrophysiology, we measured the visually evoked responses to square-wave drifting gratings in L2/3 regular-spiking (RS) neurons in control mice, -deficient mice, and mice in which was conditionally reinstated in GABAergic neurons. We found that -deficient mice exhibited enhanced pyramidal neuron excitability in vivo as well as weaker orientation tuning. These observations are the first to show alterations in cortical computation in an AS model, and they suggest a basis for cortical dysfunction in AS. Angelman syndrome (AS) is a severe neurodevelopmental disorder caused by the loss of the gene Using electrophysiological recording in vivo, we describe visual cortical dysfunctions in a mouse model of AS. Aberrant cellular properties in AS model mice could be improved by reinstating in inhibitory neurons. These findings suggest that inhibitory neurons play a substantial role in the pathogenesis of AS.
天使综合征（AS）是一种神经发育障碍，由母系遗传的UBE3A等位基因缺失引起。小鼠重现了人类AS的主要特征，并允许通过Cre重组酶的表达有条件地恢复母源UBE3A。我们最近发现，AS模型小鼠对视觉皮层第2/3层锥体神经元的抑制性驱动减弱，这导致了突触兴奋/抑制失衡。然而，这种抑制性驱动的丧失如何在体内影响神经回路仍不清楚。在这里，我们研究了单个神经元的视觉皮层反应特性，以探索UBE3A缺失对完整皮层回路和处理过程的影响。使用体内膜片钳电生理学，我们测量了对照小鼠、UBE3A缺陷小鼠以及在GABA能神经元中有条件恢复UBE3A的小鼠的第2/3层规则放电（RS）神经元对方波漂移光栅的视觉诱发反应。我们发现，UBE3A缺陷小鼠在体内表现出锥体神经元兴奋性增强以及方向调谐减弱。这些观察结果首次表明AS模型中皮层计算的改变，并为AS中的皮层功能障碍提供了一个基础。天使综合征（AS）是一种由UBE3A基因缺失引起的严重神经发育障碍。通过体内电生理记录，我们描述了AS小鼠模型中的视觉皮层功能障碍。在抑制性神经元中恢复UBE3A可以改善AS模型小鼠的异常细胞特性。这些发现表明抑制性神经元在AS的发病机制中起重要作用。
