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

视觉腹侧丘脑的细胞类型、电路和发育

• 批准号: 10751735
• 负责人: Katelyn Stebbins
• 金额: $ 4.22万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-12-25 至 2027-12-24
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751735
• 关键词: Academic Medical Centers; American; Anatomy; Area; Atlases; Axon; Behavior; Bioinformatics; Biological Models; Blindness; Brain; Brain region; Cell Maintenance; Cell Nucleus; Cells; Cues; Development; Disease; Dorsal; Economics; Embryonic Development; Emotional; Environment; Eye Movements; Fright; Genetic; Genetic Transcription; Geniculate body structure; Glaucoma; Goals; Head Movements; Image; Immunohistochemistry; Impairment; In Situ Hybridization; Individual; Injections; Interneurons; Knowledge; Lateral Geniculate Body; Light; Maintenance; Maps; Mathematics; Mediating; Molecular; Mood Disorders; Morphology; Mus; Mutant Strains Mice; Natural regeneration; Neurodegenerative Disorders; Neurodevelopmental Disorder; Neuroglia; Neurologist; Neurons; Neurophysiology - biologic function; Output; Pathway interactions; Perception; Perinatal; Play; Positioning Attribute; Process; Proteomics; Reporter; Resolution; Retina; Retinal Ganglion Cells; Rodent; Role; SHH gene; Sensory; Signal Transduction; Societies; Spatial Distribution; Specific qualifier value; Structure; Subthalamic structure; Synapses; Testing; Thalamic structure; Therapeutic Intervention; Training; Trauma; Viral; Vision; Visual; Visual Pathways; Visual System; area striata; behavioral study; career; cell type; circadian; clinical training; cohort; in vivo; inhibitory neuron; interest; light transmission; migration; morphogens; mouse model; neural circuit; neurochemistry; novel; optogenetics; progenitor; recruit; response; retinal axon; retinogeniculate; single cell sequencing; social; suprachiasmatic nucleus; tenure track; therapeutic development; transcriptomics; transmission process; vision development; visual information

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.

项目概要 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不同的 在啮齿类动物中，视网膜输入密集支配的一个主要区域是小鼠的视觉丘脑。 视觉丘脑作为理解感觉回路发育的强大模型系统，基于其 结构有序且易于实验操作。 核（LGN），分为三个不同的区域：背膝状核（dLGN），腹外侧膝状核 细胞核 (vLGN) 和 dLGN 的细胞结构和电路已得到充分研究， 众所周知，vLGN 对经典成像视觉很重要，它与非成像视觉相关。 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， 提出有关其在视觉系统中的功能作用的基本问题，并识别其结构。 与非成像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 对个人昼夜节律周期、情绪障碍、恐惧知觉和眼球运动的影响 使用最先进的单细胞来响应视觉环境的某些变化而进行头部运动。 测序和蛋白质组学，我们可以使用原位杂交鉴定 vLGN 中细胞的完整列表， 免疫组织化学和遗传报告系，我们发现亚型特异性层状分布 vLGNe 中的视网膜受体细胞是在胚胎发育过程中确定的。 对于 vLGN，研究表明至少有六种转录上不同的抑制性神经元亚型 分布到相邻的不同亚层中，使用跨突触病毒追踪，我们可以识别输入和 这些不同的 vLGN 细胞类型的输出具有细胞类型和区域特异性分辨率。 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发挥着重要作用 使用原位杂交、免疫组织化学和遗传技术开发 vLGN 中的细胞和电路。 报告线，我们可以通过视网膜和非视网膜形态发生素来测试视网膜轴突和活动的作用， 综上所述，拟议的研究不仅将鉴定 vLGN 细胞的新亚型， 但也指出了通过解剖学创建将视觉信息组织成并行路径的新方法 这种特定于亚型的感觉通道可能是理解 vLGN 的关键。 在皮层下视觉系统中接收、处理和传输光信号。 路径将给出关于如何在大脑中组织感觉信息的潜在普遍原则，并且 这将是非图像形成视觉电路的首次此类表征。