Emergence of sustained spontaneous hyperactivity and temporary preservation of OFF responses in ganglion cells of the retinal degeneration (rd1) mouse
Emergence of sustained spontaneous hyperactivity and temporary preservation of OFF responses in ganglion cells of the retinal degeneration (rd1) mouse
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DOI：
10.1152/jn.00144.2007
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发表时间：
2008-03-01
影响因子：
2.5
通讯作者：
Stasheff, Steven F.
中科院分区：
文献类型：
--
作者：
Stasheff, Steven F.
在视网膜色素变性的rd1小鼠模型中，视网膜外通路的解剖结构的复杂改变伴随着感光细胞的变性，而视网膜内神经元似乎相对保留。然而，光感受器输入的进行性丧失可能改变内层视网膜的神经回路。本研究调查了存活神经节细胞活性的变化。多电极记录监测自发和光诱发的细胞外动作电位同时从30至90视网膜神经节细胞的野生型（wt）或rd1小鼠。在rd1小鼠中，这种活动经历了三个阶段。首先，在出生后第7天（P7）观察到相关放电的正常自发“波”，并持续到睁眼后不久。第二，在P14，全场闪光引起可靠的反应，在许多细胞中，优先保存OFF响应。这些减少感光细胞变性的进展。第三，一旦光诱发反应在成年早期消失，幸存的rd1神经节细胞会以比正常高得多的自发频率放电，有时是与发育“波”不同的有节奏的爆发。“这种过度活跃一直持续到成年，在光感受器消失后的几周内。因此，当视网膜变性在rd1小鼠中进展时，视网膜内部生理学发生了显著的改变。失明发生在神经节细胞持续过度活跃的情况下，尽管这种活动，神经节细胞仍然可以存活数月。ON和OFF反应在退化的早期阶段受到不同的影响。虽然这些变化的来源仍有待了解，但在设计更有效的治疗方法时应考虑这些特征。
Complex alterations in the anatomy of outer retinal pathways accompany photoreceptor degeneration in the rd1 mouse model of retinitis pigmentosa, whereas inner retinal neurons appear relatively preserved. However, the progressive loss of photoreceptor input likely alters the neural circuitry of the inner retina. This study investigated resulting changes in the activity of surviving ganglion cells. Multi-electrode recording monitored spontaneous and light-evoked extracellular action potentials simultaneously from 30 to 90 retinal ganglion cells of wild-type (wt) or rd1 mice. In rd1 mice, this activity evolves through three phases. First, normal spontaneous "waves" of correlated firing are seen at postnatal day 7 (P7) and last until shortly after eye opening. Second, at P14, full-field light flashes evoke reliable responses in many cells, with preferential preservation of OFF responses. These diminish as photoreceptor degeneration progresses. Third, once light-evoked responses have disappeared in early adulthood, surviving rd1 ganglion cells fire at a much higher spontaneous frequency than normal, sometimes in rhythmic bursts that are distinct from the developmental "waves." This hyperactivity is sustained well into adulthood, for weeks after photoreceptors have disappeared. Thus striking alterations occur in inner retinal physiology as retinal degeneration progresses in the rd1 mouse. Blindness occurs in the face of sustained hyperactivity among ganglion cells, which remain viable for months despite this activity. ON and OFF responses are differentially affected in early stages of degeneration. While the source of these changes remains to be learned, such features should be considered in designing more effective treatments for these disorders.