Environmental Enrichment Partially Repairs Subcortical Mapping Errors in Ten-m3 Knock-Out Mice during an Early Critical Period
Environmental Enrichment Partially Repairs Subcortical Mapping Errors in Ten-m3 Knock-Out Mice during an Early Critical Period
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DOI：
10.1523/eneuro.0478-18.2019
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发表时间：
2019-11-01
期刊：
影响因子：
3.4
通讯作者：
Leamey, Catherine A.
中科院分区：
文献类型：
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作者：
Eggins, Peta;Blok, James;Leamey, Catherine A.
环境丰富（EE）已被证明可以通过调节皮质可塑性来改善神经功能。其诱导错误接线电路的功能和/或解剖修复的能力是未知的。Ten-m3基因敲除（KO）小鼠表现出高度刻板和深刻的同侧视网膜神经轴突和相关的缺陷，双眼介导的视觉行为的错误布线。我们通过分析Ten-m3 KO和野生型（WT）小鼠来确定EE是否以及何时可以驱动皮质下布线缺陷的修复，这些小鼠从成年，断奶或出生开始富集六周，与标准圈养（SE）对照组相比。6周的EE从出生开始，但不是更晚，诱导了显着减少的面积由同侧视网膜膝状体终端在科斯。在出生后第7天（P）没有观察到EE诱导的错误轴突校正，表明这种干预影响修剪而不是轴突的初始靶向。这种减少是最突出的背外侧膝状体核（dLGN）的腹外侧区，这表明最深刻的错位轴突的优先修剪。因此，EE可以部分修复特定的皮质下轴突布线缺陷，但仅在早期，发育受限的时间窗。
Environmental enrichment (EE) has been shown to improve neural function via the regulation of cortical plasticity. Its capacity to induce functional and/or anatomical repair of miswired circuits is unknown. Ten-m3 knock-out (KO) mice exhibit a highly stereotyped and profound miswiring of ipsilateral retinogeniculate axons and associated deficits in binocularly-mediated visual behavior. We determined whether, and when, EE can drive the repair of subcortical wiring deficits by analyzing Ten-m3 KO and wild-type (WT) mice that were enriched for six weeks from adulthood, weaning or birth in comparison to standard-housed (SE) controls. Six weeks of EE initiated from birth, but not later, induced a significant reduction in the area occupied by ipsilateral retinogeniculate terminals in KOs. No EE-induced correction of mistargeted axons was observed at postnatal day (P)7, indicating that this intervention impacts pruning rather than initial targeting of axons. This reduction was most prominent in the ventrolateral region of the dorsal lateral geniculate nucleus (dLGN), suggesting a preferential pruning of the most profoundly mistargeted axons. EE can thus partially repair a specific, subcortical axonal wiring deficit, but only during an early, developmentally-restricted time window.