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

项目摘要 在视觉系统中，视网膜轴突将来自外界的视觉信息传递给众多而又不同的 大脑区域。在啮齿类动物中，一个主要的区域，是密集的视网膜输入神经是视觉丘脑。鼠标 视觉丘脑作为一个强大的模型系统，在理解感觉回路的发展，基于其 有序的结构和便于实验操作。视觉丘脑，或外侧膝状体 背侧膝状体核（dorsal geniculate nucleus，dLGN），腹外侧膝状体核（ventral lateral geniculate nucleus，dLGN）， 核（vLGN）和膝状体间小叶（IGL）。dLGN的细胞结构和电路已经被充分研究， 并且已知它对于经典的成像视觉是重要的。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然没有解决， 提出了关于其在视觉系统中的功能作用的基本问题。确定结构和 与非图像形成视觉相关的神经回路的功能对于理解光如何发挥其作用至关重要。 对个体生理周期、情绪障碍、恐惧感知和眼球运动编程的影响 以及响应于视觉环境中的某些变化的头部运动。使用最先进的单细胞 通过测序和蛋白质组学，我们可以确定vLGN中细胞的全面列表。使用原位杂交， 免疫组化和遗传报告基因系，我们发现，亚型特异性层状分布的 vLGNe中的视网膜受体细胞在胚胎发育期间确定。在vLGNe中，视网膜受体部分 在vLGN中，研究表明至少有六种转录上不同的抑制性神经元亚型， 分布在相邻的亚层中。使用跨突触病毒追踪，我们可以识别输入， 这些不同的vLGN细胞类型的输出具有细胞类型和区域特异性分辨率。通过遗传 除去视觉输入，我们发现来自视网膜神经节细胞的分子线索和活动起着重要作用， vLGN细胞和电路的发展。利用原位杂交、免疫组织化学和遗传学方法， 报告线，我们可以测试的作用，视网膜轴突和活动，通过视网膜和非视网膜形态， vLGN开发。总之，拟议的研究不仅将鉴定vLGN细胞的新亚型， 还指出了一种新的方法， 不同的感觉通道这种特定于亚型的组织可能是理解vLGN如何 在皮层下视觉系统中接收、处理和传输光源信号。阐明这些 通路将提供潜在的普遍性原则，在感觉信息是如何组织在大脑中， 这将是第一次对非图像形成视觉电路进行这种表征。

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.