Dose-dependent, prion protein (PrP)-mediated facilitation of excitatory synaptic transmission in the mouse hippocampus
Dose-dependent, prion protein (PrP)-mediated facilitation of excitatory synaptic transmission in the mouse hippocampus
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DOI：
10.1007/s004240100523
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发表时间：
2001-05-01
影响因子：
4.5
通讯作者：
Lledo, PM
中科院分区：
文献类型：
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作者：
Carleton, A;Tremblay, P;Lledo, PM
多次研究表明，破坏朊病毒蛋白基因（Prnp）的两个等位基因可以消除小鼠对朊病毒疾病的易感性。然而，从朊蛋白（PrP）缺陷（Prnp(0/0)）小鼠系的表型分析中获得了相互矛盾的结果。为了探索与细胞朊病毒蛋白（PrPC）正常亚型表达或缺失相关的可能的神经生理特性，我们使用了两种独立衍生的Prnp（0/0）菌株在小鼠海马CA1区进行常规体外细胞外场电位记录。本研究分析了基础突触传递和短期形式的突触可塑性。将结果与携带野生型小鼠PrP转基因的动物进行比较，以研究PrP表达水平是否影响海马谷氨酸能突触传递。兴奋性突触传递与PrP表达有明显的相关性；即突触反应范围随着PrPC表达水平的增加而增加。另一方面，通过配对脉冲促进评估的递质释放概率似乎没有变化。有趣的是，尽管在过度表达PrPC的老年小鼠中，突触反应的总体范围仍然更大，但这些动物的这种效应似乎是由于更好的纤维募集，而不是突触传递本身的促进。综上所述，这些数据有力地证明了PrPC在调节突触传递中的功能作用。
Disruption of both alleles of the prion protein gene, Prnp, has been shown repeatedly to abolish the susceptibility of mice to developing prion diseases. However, conflicting results have been obtained from phenotypic analyses of prion protein (PrP)-deficient (Prnp(0/0)) mice lines. To explore the possible neurophysiological properties associated with expression or absence of the normal isoform of the cellular prion protein (PrPC), we used conventional in vitro extracellular field potential recordings in the hippocampal CA1 area of mice from two independently-derived Prnp(0/0) strains. Basal synaptic transmission and a short-term form of synaptic plasticity were analysed in this study. Results were compared with animals carrying a wild-type mouse PrP transgene to investigate whether PrP expression levels influence glutamatergic synaptic transmission in the hippocampus. There was a clear correlation between excitatory synaptic transmission and PrP expression; i.e. the range of synaptic responses increased with the level of PrPC expression. On the other hand, the probability of transmitter release, as assessed by paired-pulse facilitation, appeared unchanged. Interestingly, whereas the overall range for synaptic responses was still greater in older mice over-expressing PrPC, this effect in these animals appeared to be due to better recruitment of fibres rather than facilitation of synaptic transmission per se. Taken together, these data are strong evidence for a functional role for PrPC in modulating synaptic transmission.