Alzheimer's Disease Research Laboratory, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA.
Nat Neurosci. 2012 Oct;15(10):1422-9. doi: 10.1038/nn.3199. Epub 2012 Aug 26.
Experience-induced expression of immediate-early gene Arc (also known as Arg3.1) is known to be important for consolidation of memory. Using in vivo longitudinal multiphoton imaging, we found orchestrated activity-dependent expression of Arc in the mouse extrastriate visual cortex in response to a structured visual stimulation. In wild-type mice, the amplitude of the Arc response in individual neurons strongly predicted the probability of reactivation by a subsequent presentation of the same stimulus. In a mouse model of Alzheimer's disease, this association was markedly disrupted in the cortex, specifically near senile plaques. Neurons in the vicinity of plaques were less likely to respond, but, paradoxically, there were stronger responses in those few neurons around plaques that did respond. To the extent that the orchestrated pattern of Arc expression reflects nervous system responses to and physiological consolidation of behavioral experience, the disruption in Arc patterns reveals plaque-associated interference with neural network integration.
经验诱导的早期基因 Arc（也称为 Arg3.1）的表达对于记忆的巩固很重要。使用体内纵向多光子成像，我们发现小鼠外纹状视觉皮层中 Arc 的协调活动依赖性表达，以响应结构化的视觉刺激。在野生型小鼠中，单个神经元中 Arc 反应的幅度强烈预测了随后呈现相同刺激时重新激活的概率。在阿尔茨海默病的小鼠模型中，这种相关性在皮层中明显被破坏，特别是在老年斑附近。斑块附近的神经元不太可能反应，但矛盾的是，在那些确实有反应的少数斑块周围神经元中，反应更强。在协调的 Arc 表达模式反映神经系统对行为经验的反应和生理巩固的程度上，Arc 模式的中断揭示了斑块相关的神经网络整合干扰。
