Department of Biology, University of Maryland, College Park, MD 20742, USA.
Department of Biology, University of Maryland, College Park, MD 20742, USA.
Cell Rep. 2023 Feb 28;42(2):112085. doi: 10.1016/j.celrep.2023.112085. Epub 2023 Feb 7.
Binocular vision requires proper developmental wiring of eye-specific inputs to the brain. In the thalamus, axons from the two eyes initially overlap in the dorsal lateral geniculate nucleus and undergo activity-dependent competition to segregate into target domains. Here, we combine eye-specific tract tracing with volumetric super-resolution imaging to measure the nanoscale molecular reorganization of developing retinogeniculate eye-specific synapses in the mouse brain. We show there are eye-specific differences in presynaptic vesicle pool size and vesicle association with the active zone at the earliest stages of retinogeniculate refinement but find no evidence of eye-specific differences in subsynaptic domain number, size, or transsynaptic alignment across development. Genetic disruption of spontaneous retinal activity decreases retinogeniculate synapse density, delays the emergence eye-specific differences in vesicle organization, and disrupts subsynaptic domain maturation. These results suggest that activity-dependent eye-specific presynaptic maturation underlies synaptic competition in the mammalian visual system.
双眼视觉需要将特定于眼睛的输入正确地连接到大脑。在丘脑，来自双眼的轴突最初在背外侧膝状体核中重叠，并通过活动依赖性竞争来分离到目标区域。在这里，我们将眼特异性轨迹追踪与体积超分辨率成像相结合，以测量小鼠大脑中发育中的视网膜神经节眼特异性突触的纳米级分子重排。我们发现，在视网膜神经节细化的最早阶段，突触前囊泡池的大小和囊泡与活性区的关联存在眼特异性差异，但在整个发育过程中，没有证据表明亚突触域数量、大小或跨突触排列存在眼特异性差异。自发视网膜活动的遗传破坏会降低视网膜神经节突触的密度，延迟眼特异性差异的出现，影响囊泡的组织，并破坏亚突触域的成熟。这些结果表明，活动依赖性的眼特异性突触前成熟是哺乳动物视觉系统中突触竞争的基础。
