Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, Virginia 24016.
Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Blacksburg, Virginia 24061.
eNeuro. 2024 Sep 3;11(9). doi: 10.1523/ENEURO.0022-24.2024. Print 2024 Sep.
Retinal ganglion cell (RGC) axons provide direct input into several brain regions, including the dorsal lateral geniculate nucleus (dLGN), which is important for image-forming vision, and the ventrolateral geniculate nucleus (vLGN), which is associated with nonimage-forming vision. Through both activity- and morphogen-dependent mechanisms, retinal inputs play important roles in the development of dLGN, including the refinement of retinal projections, morphological development of thalamocortical relay cells (TRCs), timing of corticogeniculate innervation, and recruitment and distribution of inhibitory interneurons. In contrast, little is known about the role of retinal inputs in the development of vLGN. Grossly, vLGN is divided into two domains, the retinorecipient external vLGN (vLGNe) and nonretinorecipient internal vLGN (vLGNi). Studies previously found that vLGNe consists of transcriptionally distinct GABAergic subtypes distributed into at least four adjacent laminae. At present, it remains unclear whether retinal inputs influence the development of these cell-type-specific neuronal laminae in vLGNe. Here, we elucidated the developmental timeline for these laminae in the mouse vLGNe, and results indicate that these laminae are specified at or before birth. We observed that mutant mice without retinal inputs have a normal laminar distribution of GABAergic cells at birth; however, after the first week of postnatal development, these mutants exhibited a dramatic disruption in the laminar organization of inhibitory neurons and clear boundaries between vLGNe and vLGNi. Overall, our results show that while the formation of cell-type-specific layers in mouse vLGNe does not depend on RGC inputs, retinal signals are critical for their maintenance.
视网膜神经节细胞 (RGC) 轴突为包括背外侧膝状体核 (dLGN) 在内的多个脑区提供直接输入,dLGN 对形成图像的视觉很重要,而腹外侧膝状体核 (vLGN) 则与非图像形成视觉相关。视网膜输入通过活动依赖和形态发生依赖的机制,在 dLGN 的发育中发挥重要作用,包括视网膜投射的精细化、丘脑皮质中继细胞 (TRC) 的形态发育、皮质-膝状体神经支配的时间、抑制性中间神经元的募集和分布。相比之下,关于视网膜输入在 vLGN 发育中的作用知之甚少。大体上,vLGN 分为两个区域,即接受视网膜输入的外部 vLGN (vLGNe) 和不接受视网膜输入的内部 vLGN (vLGNi)。先前的研究发现,vLGNe 由转录上不同的 GABA 能亚型组成,分布在至少四个相邻的层中。目前,尚不清楚视网膜输入是否会影响 vLGNe 中这些细胞类型特异性神经元层的发育。在这里,我们阐明了小鼠 vLGNe 中这些层的发育时间表,结果表明这些层在出生时或出生前就已确定。我们观察到,没有视网膜输入的突变小鼠在出生时具有 GABA 能细胞正常的层状分布;然而,在出生后的第一周后,这些突变体表现出抑制性神经元层状组织的明显破坏,以及 vLGNe 和 vLGNi 之间的清晰边界。总体而言,我们的结果表明,虽然小鼠 vLGNe 中细胞类型特异性层的形成不依赖于 RGC 输入,但视网膜信号对于它们的维持至关重要。