Characterization of altered intrinsic excitability in hippocampal CA1 pyramidal cells of the Aβ-overproducing PDAPP mouse.
Characterization of altered intrinsic excitability in hippocampal CA1 pyramidal cells of the Aβ-overproducing PDAPP mouse.
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DOI：
10.1016/j.neuropharm.2013.09.004
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发表时间：
2014-04
影响因子：
4.7
通讯作者：
Randall AD
中科院分区：
文献类型：
--
作者：
Kerrigan TL;Brown JT;Randall AD
在CNS中积累Aβ肽的转基因小鼠通常用于询问阿尔茨海默病相关淀粉样蛋白病的功能后果。除了突触功能的变化，也有越来越多的证据表明，神经元的内在兴奋性的变化，可以出现在这些模型的淀粉样蛋白病。此外，这些内在特性的改变中的一些可能在实验性淀粉样蛋白病的年龄相关进展中相对早期发生。在这里，我们报告了一个详细的比较野生型（WT）和PDAPP小鼠海马CA 1区锥体神经元的内在兴奋性。后者是一种成熟的Aβ蓄积模型，表达携带印第安纳州（V717 F）突变的人APP。在本研究中使用的年龄（9-10个月），PDAPP小鼠的CNS Abeta升高，但不存在显著的斑块病理学。PDAPP小鼠在阈下固有特性，包括静息电位，输入电阻，膜时间常数和下垂没有表现出差异。当PDAPP小鼠的CA 1细胞给予不同幅度的去极化刺激时，它们最初以比WT细胞更高的频率发射。与此相对应，PDAPP细胞表现出更大的快速后去极化电位。PDAPP小鼠的动作电位峰电位窄，但动作电位阈值、上升速率和峰电位无差异。因此，并非我们先前淀粉样蛋白病模型研究中观察到的所有变化都存在于PDAPP小鼠中;然而，更窄的尖峰、更大的ADP和以更高频率发射的倾向与我们先前的工作一致，因此可能代表了淀粉样蛋白病的稳健的、跨模型的指数。本文是题为“神经发育障碍”的特刊的一部分。将PDAPP小鼠中CA 1锥体的内在兴奋性与对照进行比较。阈下固有特性是独立的基因型。当第一次去极化时，PDAPP细胞比对照组更快地激发动作电位。PDAPP小鼠的动作电位比对照组窄。
Transgenic mice that accumulate Aβ peptides in the CNS are commonly used to interrogate functional consequences of Alzheimer's disease-associated amyloidopathy. In addition to changes to synaptic function, there is also growing evidence that changes to intrinsic excitability of neurones can arise in these models of amyloidopathy. Furthermore, some of these alterations to intrinsic properties may occur relatively early within the age-related progression of experimental amyloidopathy. Here we report a detailed comparison between the intrinsic excitability properties of hippocampal CA1 pyramidal neurones in wild-type (WT) and PDAPP mice. The latter is a well-established model of Aβ accumulation which expresses human APP harbouring the Indiana (V717F) mutation. At the age employed in this study (9–10 months) CNS Abeta was elevated in PDAPP mice but significant plaque pathology was absent. PDAPP mice exhibited no differences in subthreshold intrinsic properties including resting potential, input resistance, membrane time constant and sag. When CA1 cells of PDAPP mice were given depolarizing stimuli of various amplitudes they initially fired at a higher frequency than WT cells. Commensurate with this, PDAPP cells exhibited a larger fast afterdepolarizing potential. PDAPP mice had narrower spikes but action potential threshold, rate of rise and peak were not different. Thus not all changes seen in our previous studies of amyloidopathy models were present in PDAPP mice; however, narrower spikes, larger ADPs and the propensity to fire at higher frequencies were consistent with our prior work and thus may represent robust, cross-model, indices of amyloidopathy. This article is part of a Special Issue entitled ‘Neurodevelopment Disorder’. Intrinsic excitability of CA1 pyramids in PDAPP mice were compared to controls. Subthreshold intrinsic properties were independent of genotype. When first depolarized PDAPP cells fired action potentials faster than controls. Action potentials in PDAPP mice were narrower than those in controls.
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影响因子：
6.1
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.0600948103
发表时间：
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影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
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