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P23H 大鼠视网膜感光细胞丧失后晚期的组织学和功能变化。

Late histological and functional changes in the P23H rat retina after photoreceptor loss.

机构信息

INSERM, UMR_S968, Institut de la Vision, F-75012, Paris.

出版信息

Neurobiol Dis. 2010 Apr;38(1):47-58. doi: 10.1016/j.nbd.2009.12.025. Epub 2010 Jan 7.

Abstract

Several strategies have been proposed to restore useful vision following photoreceptor degeneration. However, a very few studies have investigated late anatomical changes and functional state of residual retinal neurons after complete photoreceptor loss. We investigated the progressive degeneration of retinal ganglion cells (RGCs) in P23H rats. The RGC multielectrode array recordings indicated lower firing rates, disappearance of broad-scale, and maintenance of short-scale pairwise correlations. Up to 11% of RGCs displayed repetitive and often correlated spike discharges, reminiscent of developmental rhythmic activity, which could be reversibly suppressed by blockade of the AMPA/kainite glutamate receptors. RGCs in P23H rats remain sensitive to local electrical stimulation, generating short-latency responses as in the normal retina. These results provide evidence that, despite the demonstrated RGC degeneration, remaining active RGCs maintain their basic physiological and network properties with some emerging functional changes such as the spontaneous rhythmic activity in late stages of the degenerative disease.

摘要

已经提出了几种策略来恢复光感受器退化后的有用视力。然而,很少有研究调查完全丧失光感受器后残余视网膜神经元的晚期解剖变化和功能状态。我们研究了 P23H 大鼠视网膜神经节细胞 (RGC) 的进行性退化。RGC 多电极阵列记录显示,放电率降低,宽尺度消失,短尺度成对相关性维持。多达 11%的 RGC 显示重复且经常相关的尖峰放电,类似于发育性节律活动,这种活动可以通过阻断 AMPA/ kainite 谷氨酸受体而可逆地抑制。P23H 大鼠的 RGC 仍然对局部电刺激敏感,产生与正常视网膜相同的短潜伏期反应。这些结果表明,尽管已经证明 RGC 退化,但仍然活跃的 RGC 保持其基本的生理和网络特性,具有一些新出现的功能变化,例如退行性疾病晚期的自发节律活动。

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