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

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.