Cell types, circuitry, and development of the visual ventral thalamus

项目总结 在视觉系统中，视网膜轴突将来自外部世界的视觉信息传递给众多不同的人 大脑区域。在啮齿动物中，视网膜输入密集支配的一个主要区域是视觉丘脑。小白鼠 视觉丘脑是理解感觉回路发育的一个强大的模型系统，基于其 结构整齐，便于实验操作。视丘脑，或外侧膝状体 核(LGN)，分为三个不同的区域：背膝状核(DLGN)，腹侧膝状体 核团(VLGN)和膝间小叶(IGL)。对dLGN的细胞结构和电路进行了深入的研究， 众所周知，这对经典的成像视觉很重要。VLGN与非成像相关 视觉及其完整的神经化学、细胞结构和视网膜丘脑连接仍未解决， 提出了关于它在视觉系统中的功能作用的根本问题。识别结构和 与非成像视觉相关的神经回路的功能对于理解光是如何发挥其作用至关重要 对个人昼夜节律、情绪障碍、恐惧感知和眼动的影响 以及响应视觉环境中的某些变化的头部运动。使用最先进的单电池 通过测序和蛋白质组学分析，我们可以确定vLGN中的细胞的全面列表。利用原位杂交， 免疫组织化学，以及遗传报告系，我们发现亚型特异性的板层分布 VLGNe中的视网膜脱离细胞是在胚胎发育过程中确定的。在vLGNe中，视网膜的主要部分 对于vLGN，研究表明至少有六种转录上不同的抑制神经元亚型是 分布在不同的相邻亚胺中。使用跨突触病毒追踪，我们可以识别输入和 这些不同的vLGN单元类型的输出具有单元类型和区域特定分辨率。由基因决定的 除去视觉输入，我们发现视网膜神经节细胞的分子线索和活动起着重要作用 在vLGN中的单元和电路的发展中。利用原位杂交、免疫组织化学和遗传学 记者线，我们可以测试视网膜轴突的作用和活动，通过视网膜和非视网膜的形态原，在 VLGN开发。综上所述，拟议的研究不仅将识别vLGN细胞的新亚型， 但也指出了通过解剖创建将视觉信息组织成平行路径的新方法 不同的感官通道。此子类型特定的组织可能是理解vLGN如何 在皮质下视觉系统中接收、处理和发送来自光的信号。澄清这些问题 通路将在大脑中如何组织感觉信息方面给出潜在的概括性原则，以及 这将是第一次对非成像视觉回路进行这样的描述。

PROJECT SUMMARY In the visual system, retinal axons convey visual information from the outside world to numerous and distinct brain regions. In rodents, one major area that is densely innervated by retinal input is the visual thalamus. Mouse visual thalamus serves as a powerful model system in understanding sensory circuit development, based on its orderly structure and ease of accessibility for experimental manipulation. Visual thalamus, or lateral geniculate nucleus (LGN), is divided into three distinct regions: dorsal geniculate nucleus (dLGN), ventral lateral geniculate nucleus (vLGN), and the intergeniculate leaflet (IGL). Cytoarchitecture and circuitry of dLGN are well-studied, and it is known to be important for classical image-forming vision. vLGN is associated with non-image-forming vision and its complete neurochemistry, cytoarchitecture, and retinothalamic connectivity remain unresolved, raising fundamental questions about its functional role within the visual system. Identifying the structure and function of neural circuits related to non-image-forming vision is crucial for understanding how light exerts its influence on programming an individual’s circadian cycle, mood disorders, fear perception, and eye movement and head movement in response to certain changes in the visual environment. Using state-of-the-art single-cell sequencing and proteomics, we can identify a comprehensive list of the cells in vLGN. Using in situ hybridization, immunohistochemistry, and genetic reporter lines, we found that the subtype-specific laminar distribution of retinorecipient cells in vLGNe is determined during embryonic development. In vLGNe, the retinorecipient portion of vLGN, studies have demonstrated at least six transcriptionally distinct subtypes of inhibitory neurons that are distributed into distinct adjacent sublaminae. Using trans-synaptic viral tracing, we can identify the inputs and outputs of these distinct vLGN cell types with both cell type- and region-specific resolution. By genetically removing visual input, we found that molecular cues and activity from retinal ganglion cells play important roles in the development of cells and circuits in vLGN. Using in situ hybridization, immunohistochemistry, and genetic reporter lines, we can test the role of retinal axons and activity, through retinal and non-retinal morphogens, in vLGN development. Taken together, the proposed studies will not only identify novel subtypes of vLGN cells, but also point to new means of organizing visual information into parallel pathways by anatomically creating distinct sensory channels. This subtype-specific organization may be key to understanding how the vLGN receives, processes, and transmits light-derived signals in the subcortical visual system. Elucidating these pathways will give potentially generalizable principles in how sensory information is organized in the brain, and this would be the first such characterization of non-image-forming visual circuits.