BACKGROUND The dorsal lateral geniculate nucleus (dLGN) of the mouse has become a model system for understanding thalamic circuit assembly. While the development of retinal projections to dLGN has been a topic of extensive inquiry, how and when nonretinal projections innervate this nucleus remains largely unexplored. In this study, we examined the development of a major nonretinal projection to dLGN, the ascending input arising from cholinergic neurons of the brainstem. To visualize these projections, we used a transgenic mouse line that expresses red fluorescent protein exclusively in cholinergic neurons. To assess whether retinal input regulates the timing and pattern of cholinergic innervation of dLGN, we utilized the math5-null (math5-/-) mouse, which lacks retinofugal projections due to a failure of retinal ganglion cell differentiation. RESULTS Cholinergic brainstem innervation of dLGN began at the end of the first postnatal week, increased steadily with age, and reached an adult-like pattern by the end of the first postnatal month. The absence of retinal input led to a disruption in the trajectory, rate, and pattern of cholinergic innervation of dLGN. Anatomical tracing experiments reveal these disruptions were linked to cholinergic projections from parabigeminal nucleus, which normally traverse and reach dLGN through the optic tract. CONCLUSIONS The late postnatal arrival of cholinergic projections to dLGN and their regulation by retinal signaling provides additional support for the existence of a conserved developmental plan whereby retinal input regulates the timing and sequencing of nonretinal projections to dLGN.

中文翻译：

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视网膜输入的缺乏破坏了小鼠背外侧膝状核中胆碱能脑干投射的发展。

背景技术小鼠的背外侧膝状核（dLGN）已经成为用于理解丘脑回路组装的模型系统。尽管将视网膜投射发展为dLGN一直是一个广泛的研究课题，但非视网膜投射如何以及何时使该核受神经支配仍大有待探索。在这项研究中，我们研究了dLGN的主要非视网膜投影的发展，dLGN是脑干胆碱能神经元引起的上升输入。为了可视化这些预测，我们使用了仅在胆碱能神经元中表达红色荧光蛋白的转基因小鼠品系。为了评估视网膜输入是否调节dLGN的胆碱能神经支配的时间和模式，我们利用了math5-null（math5-/-）小鼠，该小鼠由于视网膜神经节细胞分化失败而缺乏视网膜视网膜上的突起。结果dLGN的胆碱能脑干神经支配在产后第一周结束时开始，随着年龄的增长而稳定增加，并在产后第一个月末达到类似成人的模式。视网膜输入的缺乏导致dLGN的胆碱能神经支配的轨迹，速率和模式的破坏。解剖学追踪实验表明，这些破坏与双双旁核的胆碱能投射有关，该双核通常穿过视线并到达dLGN。结论产后胆碱能投射到dLGN的后期到达以及它们通过视网膜信号的调控为保守的发展计划的存在提供了额外的支持，其中视网膜输入调节了非视网膜投射到dLGN的时间和顺序。