Maatuf Yossi, Stern Edward A, Slovin Hamutal
The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002 Israel.
The Gonda Multidisciplinary Brain Research Center, Bar-Ilan University, Ramat Gan, 5290002 Israel.
Sci Rep. 2016 Apr 15;6:24560. doi: 10.1038/srep24560.
Alzheimer's disease (AD) is the most common form of dementia. One of the neuropathological hallmarks of AD is the accumulation of amyloid-β plaques. Overexpression of human amyloid precursor protein in transgenic mice induces hippocampal and neocortical amyloid-β accumulation and plaque deposition that increases with age. The impact of these effects on neuronal population responses and network activity in sensory cortex is not well understood. We used Voltage Sensitive Dye Imaging, to investigate at high spatial and temporal resolution, the sensory evoked population responses in the barrel cortex of aged transgenic (Tg) mice and of age-matched non-transgenic littermate controls (Ctrl) mice. We found that a whisker deflection evoked abnormal sensory responses in the barrel cortex of Tg mice. The response amplitude and the spatial spread of the cortical responses were significantly larger in Tg than in Ctrl mice. At the network level, spontaneous activity was less synchronized over cortical space than in Ctrl mice, however synchronization during evoked responses induced by whisker deflection did not differ between the two groups. Thus, the presence of elevated Aβ and plaques may alter population responses and disrupts neural synchronization in large-scale networks, leading to abnormalities in sensory processing.
阿尔茨海默病（AD）是最常见的痴呆形式。AD的神经病理学特征之一是β-淀粉样蛋白斑块的积累。在转基因小鼠中，人淀粉样前体蛋白的过度表达会诱导海马体和新皮质中β-淀粉样蛋白的积累以及斑块沉积，且这种沉积会随着年龄增长而增加。这些影响对感觉皮层中神经元群体反应和网络活动的作用尚不清楚。我们使用电压敏感染料成像技术，以高空间和时间分辨率研究了老年转基因（Tg）小鼠和年龄匹配的非转基因同窝对照（Ctrl）小鼠桶状皮层中的感觉诱发群体反应。我们发现，触须偏转在Tg小鼠的桶状皮层中诱发了异常的感觉反应。Tg小鼠的反应幅度和皮层反应的空间扩散明显大于Ctrl小鼠。在网络层面上，与Ctrl小鼠相比，自发活动在皮层空间上的同步性较低，然而，触须偏转诱发反应期间两组之间的同步性没有差异。因此，β-淀粉样蛋白水平升高和斑块的存在可能会改变群体反应并破坏大规模网络中的神经同步，从而导致感觉处理异常。
