Laboratorio de Circuitos Corticales, Centro de Tecnología Biomédica, Universidad Politécnica de Madrid Madrid, Spain.
Front Neuroanat. 2009 Nov 20;3:28. doi: 10.3389/neuro.05.028.2009. eCollection 2009.
One of the main pathological hallmarks of Alzheimer's disease (AD) is the accumulation of plaques in the cerebral cortex, which may appear either in the neuropil or in direct association with neuronal somata. Since different axonal systems innervate the dendritic (mostly glutamatergic) and perisomatic (mostly GABAergic) regions of neurons, the accumulation of plaques in the neuropil or associated with the soma might produce different alterations to synaptic circuits. We have used a variety of conventional light, confocal and electron microscopy techniques to study their relationship with neuronal somata in the cerebral cortex from AD patients and APP/PS1 transgenic mice. The main finding was that the membrane surfaces of neurons (mainly pyramidal cells) in contact with plaques lack GABAergic perisomatic synapses. Since these perisomatic synapses are thought to exert a strong influence on the output of pyramidal cells, their loss may lead to the hyperactivity of the neurons in contact with plaques. These results suggest that plaques modify circuits in a more selective manner than previously thought.
阿尔茨海默病（AD）的主要病理学特征之一是大脑皮层中斑块的积累，这些斑块可能出现在神经间质中，也可能直接与神经元胞体相关联。由于不同的轴突系统支配神经元的树突（主要是谷氨酸能）和胞体周围（主要是 GABA 能）区域，因此斑块在神经间质中的积累或与胞体相关联可能会对突触回路产生不同的改变。我们使用了各种常规的光镜、共聚焦和电子显微镜技术来研究它们与 AD 患者和 APP/PS1 转基因小鼠大脑皮层中神经元胞体的关系。主要发现是，与斑块接触的神经元（主要是锥体细胞）的膜表面缺乏 GABA 能胞体周围的突触。由于这些胞体周围的突触被认为对锥体细胞的输出有很强的影响，它们的缺失可能导致与斑块接触的神经元过度活跃。这些结果表明，与之前的想法相比，斑块以更具选择性的方式修饰回路。
