Stebbins Katelyn, Somaiya Rachana Deven, Sabbagh Ubadah, Liang Yanping, Su Jianmin, Fox Michael A
bioRxiv. 2024 Jan 15:2024.01.12.575402. doi: 10.1101/2024.01.12.575402.
Retinal ganglion cell (RGC) axons provide direct input into several nuclei of the mouse visual thalamus, including the dorsal lateral geniculate nucleus (dLGN), which is important for classical image-forming vision, and the ventral lateral geniculate nucleus (vLGN), which is associated with non-image-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), the timing of corticogeniculate innervation, and the recruitment of inhibitory interneurons from progenitor zones. 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 the non-retinorecipient internal vLGN (vLGNi). We previously found that vLGNe consists of transcriptionally distinct GABAergic subtypes that are distributed into at least four adjacent laminae. At present, it remains unclear whether retinal inputs influence the development of these cell-specific neuronal laminae in vLGNe. Here, we elucidated the developmental timeline for the formation and maintenance of these laminae in the mouse vLGNe and results indicate that these laminae are specified at or before birth, well before eye-opening and the emergence of experience-dependent visual activity. 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 vLGNe does not depend on RGC inputs, retinal signals are critical for their maintenance.
视网膜神经节细胞（RGC）轴突直接投射到小鼠视觉丘脑的多个核团，包括对经典成像视觉很重要的背外侧膝状体核（dLGN），以及与非成像视觉相关的腹外侧膝状体核（vLGN）。通过活动依赖和形态发生素依赖机制，视网膜输入在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以及从祖细胞区募集抑制性中间神经元。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，接受视网膜投射的外侧vLGN（vLGNe）和不接受视网膜投射的内侧vLGN（vLGNi）。我们之前发现，vLGNe由转录上不同的GABA能亚型组成，这些亚型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中这些层形成和维持的发育时间线，结果表明这些层在出生时或出生前就已确定，远在睁眼和经验依赖的视觉活动出现之前。我们观察到，没有视网膜输入的突变小鼠在出生时GABA能细胞的层状分布正常；然而，在出生后第一周的发育之后，这些突变体在抑制性神经元的层状组织以及vLGNe和vLGNi之间的清晰边界上表现出显著破坏。总体而言，我们的结果表明，虽然vLGNe中细胞类型特异性层的形成不依赖于RGC输入，但视网膜信号对其维持至关重要。
