期刊
JOURNAL OF NEUROSCIENCE
卷 28, 期 28, 页码 7091-7103出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0409-08.2008
关键词
cerebellum; granule cell; prion; LTP; action potential; motor control
Although the role of abnormal prion protein (PrP) conformation in generating infectious brain diseases (transmissible spongiform encephalopathy) has been recognized, the function of PrP in the normal brain remains mostly unknown. In this investigation, we considered the effect of PrP gene knock-out (PrP0/0) on cerebellar neural circuits and in particular on granule cells, which show intense PrP expression during development and selective affinity for PrP. At the third postnatal week, whenPrP expression would normally attain mature levels, PrP0/0 mice showed low performance in the accelerating rotarod and runway tests and the functioning of 40% of granule cells was abnormal. Spikes were slow, nonovershooting, and nonrepetitive in relation with a reduction in transient inward and outward membrane currents, and also the EPSPs and EPSCs had slow kinetics. Overall, these alterations closely resembled an immature phenotype. Moreover, in slow-spiking PrP0/0 granule cells, theta-burst stimulation was unable to induce any long-term potentiation. This profound impairment in synaptic excitation and plasticity was associated with a protracted proliferation of granule cells and disappeared at P40-P50 along with the recovery of normal motor behavior (Bureler et al., 1992). These results suggest that PrP plays an important role in granule cell development eventually regulating cerebellar network formation and motor control.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据